Studying changes in DNA for causes of cancer

Studying changes in DNA for causes of cancer

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First of all let me say that I'm not into Biology myself… but I have a question for those of you who are.

From what I've read, cancer is caused by 'faulty' DNA that behaves abnormally. Mutations can occur for various reasons, ranging from simple 'copying errors' to environmental factors.

I was just wondering whether current research has dealt with storing DNA of people or animals (e.g. rodents) and observing how it changed, especially for cases where it eventually resulted in cancer. Something along the lines of this, but I'd like to know what research has actually been done so far.

I tried to comment but what I wrote is too long, so here it is as an answer of sorts.

If I understand the question, you are asking: has anyone done a prospective study where they store the DNA of individuals and then later, when some of these individuals get cancer, have a look for mutations that are associated with that cancer. In fact this is done all of the time, but it isn't necessary to store any DNA because the cancer patients will have the normal sequence in all of their non cancerous tissues - only the cancer cells will have the relevant mutations. See here for a recent example of this type of study that made the news.

Your BBC link is to a story in which the genomes of people will be analysed to determine if there are genetic factors which predispose them to cancer (and other diseases), but these won't be the mutations that actually create the cancerous cells.

There is a tremendous amount of information relating to mutations of genes and how they produce cancer. In fact, this is multi-billion area of research.

What is even more interesting, is the aneuploidy hypothesis of cancer, in which it is chromosomal abnormalities, rather than mutations in single genes, that lead to cancer.

I suggest reading about it, there was an article by Peter Deusberg in a 2007 Scientific American article.

Changes in genes involved in DNA repair and packaging linked to risk of multiple myeloma

Researchers have identified two gene regions that contribute to multiple myeloma, an inherited cancer that occurs in bone marrow, through a new method that makes use of human disease pedigrees. Nicola Camp and Rosalie Waller of the Huntsman Cancer Institute at the University of Utah, and colleagues, report their findings February 1st, 2018, in PLOS Genetics.

Human pedigrees can help geneticists to track diseases through different branches of a family tree and pinpoint the mutations that are responsible. This process is straightforward in diseases caused by a mutation in a single gene, but for complex diseases, which involve multiple genes, the use of pedigrees has not been so effective. In the current study, researchers developed a new method to analyze high-risk pedigrees (large, multi-generational families with more affected members than would be expected by chance) to identify shared regions of the genome that likely harbor disease-causing genes. They applied the method using pedigrees from 11 Utah families at risk of multiple myeloma, a complex, heritable cancer that causes malignant immune cells to proliferate in the bone marrow. The analysis revealed two regions that may contribute to the disease: one involved in regulating DNA repair, and the other, a key gene involved in packaging DNA inside the cell's nucleus.

The myeloma findings from the new study demonstrate that high-risk pedigrees, a classic design for straightforward diseases, can also be successful for pinning down genes that contribute to complex diseases with appropriate analytics. This new strategy may be helpful for narrowing in on the genetic causes underlying other common yet complex diseases, such as obesity, diabetes and Alzheimer's disease.

Nicola Camp adds: "We are very encouraged by the new method. It certainly plays to the strengths of the large Utah pedigrees, revitalizing the family design for complex diseases. As we did in this study, the focused regions can be further investigated in smaller families to find genes and specific mutations. The method can be used for any complex disease. We are already pursuing large pedigrees in several other domains, including other cancers, psychiatric disorders, birth defects, and pre-term birth phenotypes, with several more genome-wide significant regions found. We're excited about the potential."

How infectious agents cause cancer

The major mechanisms by which infectious agents can promote and maintain tumor formation can be divided broadly into three main categories (Figure 2). The first is the induction of chronic inflammation as a result of a continuing immune response to a persistent infection. This occurs, for example, in the case of hepatitis C virus (HCV), associated with liver cancer, which continually replicates in the liver, setting up a chronic state of inflammation there. Similarly, the blood fluke Schistosoma haematobium and the Gram-negative bacterium Helicobacter pylori can both directly contribute to cancer formation through persistence within the host causing chronic inflammation [4]. H. pylori is a good example of this category, and was classified by the World Health Organization as a class 1 carcinogen in 1994. There is a high prevalence of persistent infection with H. pylori: worldwide, 75% of people are infected, with prevalence being higher in sub-Saharan Africa, where H. pylori is associated with 63.4% of all stomach cancers [1]. However, the fact that not all people infected with H. pylori develop gastric cancer clearly shows that the infectious agent is a risk factor, but that other environmental and genetic influences are involved in cancer formation.

Infectious agents can contribute to malignant transformation by several mechanisms. These can be broadly divided into: chronic inflammation, which drives abnormal levels of cell proliferation (yellow) direct virus-induced transformation of infected cells, leading to increased cell survival (red) and immunosuppression, which allows the pathogen to evade the immune system and persist (blue). The colour coding is maintained from Figure 1. Chronic inflammation leads to the production of inflammatory cytokines as well as reactive oxygen and nitrogen oxide species (ROS and RNOS) by phagocytes at the site of infection, which can lead to DNA damage as well as cellular damage and increased cell cycling. Virus-induced transformation is caused by the actions of pathogen-encoded oncogenic proteins as well as by integration into the host genome (HPV). The transforming events outlined in this figure do not necessarily lead directly to cancer formation for example, despite encoding similar proteins, other infectious agents do not cause cancer. The fact that some pathogens have evolved to persist without causing tumorigenesis also highlights that persistence is maybe a prerequisite for, but is on its own insufficient for, oncogenesis in humans. Immune evasion mechanisms include control of the adaptive and innate immune system, allowing avoidance of tumor surveillance. EBV, Epstein-Barr virus HBV, human hepatitis virus B HCV, hepatitis virus C HIV, human immunodeficiency virus HPV, human papillomavirus HTLV-1, human T-lymphotropic virus 1 KSHV, Kaposi sarcoma-associated herpesvirus.

Second, oncogenesis can occur through virus-induced transformation. This is due to the persistence of the viral genome in a latent form in an infected cell, either without replication, as with Epstein-Barr virus (EBV), which infects B lymphocytes, or through integration of the viral genome into a host-cell chromosome, as with human papillomavirus (HPV), the cause of cervical cancer. EBV is frequently detected in childhood Burkitt's lymphoma, post-transplant B-cell lymphomas, non-Hodgkin's lymphoma, Hodgkin's disease and nasopharyngeal carcinoma [1]. The transforming capability of this virus is exemplified further by its ability to transform resting B cells in vitro at high efficiency to obtain stable proliferating lymphoblastoid cell lines. This process is driven by EBV-encoded latent proteins that directly promote cell growth and survival – for example, lymphocyte membrane-associated protein-1 (LMP-1) .

The third mechanism is the chronic suppression of the immune system by the infectious agent, such as the immunodeficiency (AIDS) caused by HIV infection. The presence of natural mechanisms of immunosurveillance for cancer cells, which in the case of an infectious etiology will also involve immune mechanisms that routinely control the infection, suggests why pathogens with oncogenic potential do not rapidly cause malignancy. A compromised immune system can result in an increased incidence of infection-driven tumors by weakening the immune control. Such an increase is seen, for example, in transplant patients, who are being treated with immunosuppressants, or in individuals with AIDS [5].

Pathogens associated with cancer exemplify many of these mechanisms persistent infection involves evading the immune response as well as chronic inflammation, which even in the immune-competent leads to chronic cell proliferation and a greater risk of oncogenic transformation. However, many non-oncogenic pathogens are equally adept at these processes, indicating that other factors must be involved. For example, the risk of an infectious agent causing cancer may also depend on the cell type infected, as certain cell lineages could be more 'prone' to transformation than others. For example, the increased prevalence of lympho mas and leukemias in children and young adults suggests that lymphocytes are more susceptible to transformation.

The molecular biology of cancer

The process by which normal cells become progressively transformed to malignancy is now known to require the sequential acquisition of mutations which arise as a consequence of damage to the genome. This damage can be the result of endogenous processes such as errors in replication of DNA, the intrinsic chemical instability of certain DNA bases or from attack by free radicals generated during metabolism. DNA damage can also result from interactions with exogenous agents such as ionizing radiation, UV radiation and chemical carcinogens. Cells have evolved means to repair such damage, but for various reasons errors occur and permanent changes in the genome, mutations, are introduced. Some inactivating mutations occur in genes responsible for maintaining genomic integrity facilitating the acquisition of additional mutations. This review seeks first to identify sources of mutational damage so as to identify the basic causes of human cancer. Through an understanding of cause, prevention may be possible. The evolution of the normal cell to a malignant one involves processes by which genes involved in normal homeostatic mechanisms that control proliferation and cell death suffer mutational damage which results in the activation of genes stimulating proliferation or protection against cell death, the oncogenes, and the inactivation of genes which would normally inhibit proliferation, the tumor suppressor genes. Finally, having overcome normal controls on cell birth and cell death, an aspiring cancer cell faces two new challenges: it must overcome replicative senescence and become immortal and it must obtain adequate supplies of nutrients and oxygen to maintain this high rate of proliferation. This review examines the process of the sequential acquisition of mutations from the prospective of Darwinian evolution. Here, the fittest cell is one that survives to form a new population of genetically distinct cells, the tumor. This review does not attempt to be comprehensive but identifies key genes directly involved in carcinogenesis and demonstrates how mutations in these genes allow cells to circumvent cellular controls. This detailed understanding of the process of carcinogenesis at the molecular level has only been possible because of the advent of modern molecular biology. This new discipline, by precisely identifying the molecular basis of the differences between normal and malignant cells, has created novel opportunities and provided the means to specifically target these modified genes. Whenever possible this review highlights these opportunities and the attempts being made to generate novel, molecular based therapies against cancer. Successful use of these new therapies will rely upon a detailed knowledge of the genetic defects in individual tumors. The review concludes with a discussion of how the use of high throughput molecular arrays will allow the molecular pathologist/therapist to identify these defects and direct specific therapies to specific mutations.

Sloan Kettering Institute Researchers Look Beyond DNA to Identify Cancer Drivers

Bottom Line: Researchers at the Sloan Kettering Institute have found that changes in an information-carrying molecule called messenger RNA (mRNA) can inactivate the functions of tumor suppressor genes and thereby promote cancer. The findings pinpoint previously unknown drivers of the disease, indicating that cancer diagnostics need to go beyond the analysis of DNA mutations.

Background: Most people think of cancer as a disease of disorderly DNA. Mutations in the sequence of DNA alter the function of the proteins made from that DNA, leading to uncontrolled cell division. But between DNA and proteins is another layer of information, mRNA, which serves as a crucial link between the two.

Findings and Method: New findings from molecular biologist Christine Mayr, MD, PhD, and colleagues at the Sloan Kettering Institute suggest that many of the mRNAs in cancer cells produce truncated tumor-suppressor proteins which have cancer promoting functions. The changes occur not only in known tumor-suppressor genes but also in previously unrecognized ones. Because genetic tests don&rsquot usually look at mRNA, those changes have gone undetected by cancer doctors so far. Based on these findings, cancer diagnostics may need to change to include these previously unknown cancer drivers.

Dr. Mayr&rsquos team looked specifically at chronic lymphocytic leukemia (CLL), a type of blood cancer. Her colleague at Memorial Sloan Kettering Cancer Center, physician-scientist Omar Abdel-Wahab, MD, supplied them with blood samples from people with the condition. Using a method that Dr. Mayr&rsquos lab developed to detect these particular mRNA changes, they found that a substantially greater number of people with CLL had an inactivation of a tumor suppressor gene at the mRNA level than those who had it at the DNA level.

These findings help explain a long-standing conundrum, which is that CLL cells have relatively few known DNA mutations. Some CLL cells lack even those known mutations. In effect, the mRNA changes that Dr. Mayr&rsquos team discovered could account for the missing DNA mutations. Because CLL is such a slow-growing cancer and people with CLL often live for many years, it&rsquos too early to say whether these mRNA changes are associated with a poorer prognosis.

Though Dr. Mayr&rsquos team identified the mRNA changes in CLL, they&rsquore likely not limited to this blood cancer. The team found them in samples of T cell acute lymphocytic leukemia too, for example. Other researchers have found them in breast cancer.

Author Comments: &ldquoCurrent cancer diagnostic efforts predominantly focus on the sequencing of DNA to identify mutations,&rdquo explained Dr. Mayr. &ldquoOur study demonstrates that cancer-gained changes in mRNA processing can essentially mimic the effects of somatic mutations in DNA, pointing to the need to look past DNA for answers to questions about what causes the disease.&rdquo

Journal: &ldquoWidespread intronic polyadenylation inactivates tumor suppressor genes in leukemia&rdquo was published in Nature on August 27, 2018. Dr. Mayr, a member of the Cancer Biology and Genetics Program at the Sloan Kettering Institute, served as senior author.

Funding: This work was funded by a National Cancer Institute grant (U01-CA164190), a Starr Cancer Foundation grant, an Innovator Award of the Damon Runyon-Rachleff Cancer Foundation and the Island Outreach Foundation (DRR-24-13), a National Institutes of Health Director&rsquos Pioneer Award (DP1-GM123454), the Pershing Square Sohn Cancer Research Alliance, and an MSK Core grant (P30 CA008748).

How a Marker for Genetic Damage Changed the Study of DNA

Dr. William Bonner’s research at the NIH revolutionized the study of DNA repair by allowing scientists to detect a form of DNA damage called a double-strand break. Photo by Bill Branson.

National DNA Day, held on April 25, commemorates the completion of the Human Genome Project in 2003 and the day in 1953 when a research team led by Drs. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin published their groundbreaking paper on the structure of DNA in the journal Nature.

The mapping of DNA’s structure opened the door to modern genetics and our current understanding of how DNA affects the health and survival of all living things. Since then, there have been numerous additional major leaps forward in the field of genetics. Among them was the discovery of a universal hallmark of DNA damage by IRP Scientist Emeritus William Bonner, Ph.D., an advance that revolutionized the study of how cells sense and repair genetic defects. Dr. Bonner’s findings paved the way for a deeper understanding of cell biology, as well as clinical advances for treating cancer and for assessing risks from radiation in the environment.

When Dr. Bonner came to the NIH in 1974, he brought with him a keen interest in histones, the proteins that DNA coils around so it can fit inside the cell nucleus. In 1980, while working at the NIH’s National Cancer Institute (NCI), he discovered two previously unnoticed variants to one of the four ‘core’ histones, known as H2A. He named these variants H2AX and H2AZ and set about trying to determine their function.

Segments of DNA wind around histones to form bundles called nucleosomes, which are squished together in a substance called chromatin in order to fit all of a cell’s DNA into its nucleus.

“My research group was one of only a handful looking at histones,” Dr. Bonner says. In fact, he remembers that histones once won a biotech company publication’s contest for the world’s most boring proteins.

Yet the new histone variants Dr. Bonner identified proved to be anything but boring. He found closely related versions of them in everything from yeast to human cells, which led him to wonder if they played an important role that had been preserved throughout evolution. Thinking that H2AX may have something to do with basic cell survival, he used various means to stress cells in order to see what would happen to H2AX. He didn’t have much luck until he exposed the cells to ionizing radiation, which induces a particularly harmful form of DNA damage called a double-strand break. When such a break occurs, it’s like losing part of the cell’s instruction manual. Regular activity breaks down, leaving the cell susceptible to the types of malfunctions that can kill cells or lead to cancer.

“It was serendipitous that we had a radiation machine in the basement,” Dr. Bonner remembers. “I could see a huge change — about fifty percent of the H2AX histones had been converted into something else.”

Dr. Bonner’s team found that the new form of H2AX induced by radiation came about due to a modification called phosphorylation. Phosphorylation happens when a chemical tag called a phosphoryl group, an electrically charged collection of oxygen and phosphorus atoms, attaches to a molecule. This often changes the molecule’s function. In the case of an H2AX histone, the presence of a double-strand break in the DNA coiled around the histone triggers a chemical reaction that causes a phosphoryl group to attach to the histone. Dr. Bonner’s team named this phosphorylated form of the histone ‘gamma-H2AX.’

Until Dr. Bonner’s discovery, which was published in 1998, it was difficult to study damaged sections of the genome. To see a double-strand break, researchers had to bombard cells with lethal doses of radiation that caused massive damage. Of course, if the cell can’t survive, it is very difficult to study cellular changes that result from non-lethal damage.

By tagging gamma-H2AX histones with a fluorescent antibody, Dr. Bonner showed that exposing cells to ionizing radiation caused hundreds of H2AX histones near the site of a double-strand break to become phosphorylated within minutes, creating a rapid and highly amplified response akin to a cellular fire alarm. At long last, scientists could finally observe non-lethal accumulations of double-strand breaks and the steps cells take to repair them under the microscope.

Dr. Bonner’s technique for tagging gamma-H2AX histones with a fluorescent molecule allows researchers to identify locations (green) in cells where DNA double-strand breaks are being repaired.

Dr. Bonner and his research team subsequently began collaborating with an NCI colleague, Andre Nussenzweig, Ph.D., to develop ‘knockout’ cells and mice that lacked H2AX histones. While these cells and animals survived, they proved to be more prone to developing mutations in their DNA after exposure to radiation, revealing that H2AX is essential for the proper repair of DNA double-strand breaks. What’s more, even when they were not exposed to radiation, the H2AX knockout mice exhibited two other problems that showed the importance of double-strand breaks that occur naturally in the body. First, the mice had generally poor health because their cells could not complete the normal DNA rearrangements necessary for a robust immune system. Second, male mice were sterile because they could not produce sperm. In this way, double-strand breaks are a double-edged sword: random, unwanted breaks can result in damaging mutations when they are repaired, but breaks formed deliberately and temporarily during certain processes are necessary for good health.

This multifaceted nature of DNA double-strand breaks makes them a topic of wide and intense scientific interest. Today, the technique that Dr. Bonner developed to detect gamma-H2AX is used to study double-strand breaks in laboratories all over the world: in basic science research, studies of disease, therapeutic development, and measurements of risk due to radiation exposure.

Dr. Bonner’s method for detecting gamma-H2AX histones has found applications in a wide range of fields, including studies of the risks faced by workers exposed to radiation.

“Many people would call me up and arrange a collaboration to see if gamma-H2AX was involved in something they were studying,” Dr. Bonner says.

For example, a researcher in England wanted to collaborate on an experiment to see if gamma-H2AX is involved in cell division. (It is.) Meanwhile, other groups are using Dr. Bonner’s technique to test whether experimental drugs damage DNA. It can also be used to assess damage to DNA in cancer patients’ blood samples to determine how well their treatment is working, since most cancer treatments work by destroying the DNA of cancer cells. The U.S. Army is even using it to study the effects of accidents that expose people to radiation.

“My goal early on in my career was to make a seminal discovery of some sort,” reflects Dr. Bonner, who is now retired but maintains an ongoing working relationship with the NIH as a Scientist Emeritus. “I did that, so yeah, I guess I reached my goal.”

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[1] GammaH2AX and cancer. Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, Solier S, Pommier Y. Nat Rev Cancer. 2008 8(12):957-67.

Genes that stop the cell multiplying (tumour suppressor genes)

It is usual for cells to repair faults in their genes. When the damage is very bad, tumour suppressor genes may stop the cell growing and dividing.

Mutations in tumour suppressor genes mean that a cell no longer understands the instruction to stop growing. The cell can then start to multiply out of control. This can lead to cancer.

The best known tumour suppressor gene is p53. Researchers know that the p53 gene is damaged or missing in most cancers.


Chromatin structure defines the state in which genetic information in the form of DNA is organized within a cell. This organization of the genome into a precise compact structure greatly influences the abilities of genes to be activated or silenced. Epigenetics, originally defined by C.H.Waddington (1) as ‘the causal interactions between genes and their products, which bring the phenotype into being’, involves understanding chromatin structure and its impact on gene function. Waddington's definition initially referred to the role of epigenetics in embryonic development however, the definition of epigenetics has evolved over time as it is implicated in a wide variety of biological processes. The current definition of epigenetics is ‘the study of heritable changes in gene expression that occur independent of changes in the primary DNA sequence’. Most of these heritable changes are established during differentiation and are stably maintained through multiple cycles of cell division, enabling cells to have distinct identities while containing the same genetic information. This heritability of gene expression patterns is mediated by epigenetic modifications, which include methylation of cytosine bases in DNA, posttranslational modifications of histone proteins as well as the positioning of nucleosomes along the DNA. The complement of these modifications, collectively referred to as the epigenome, provides a mechanism for cellular diversity by regulating what genetic information can be accessed by cellular machinery. Failure of the proper maintenance of heritable epigenetic marks can result in inappropriate activation or inhibition of various signaling pathways and lead to disease states such as cancer (2,3).

Recent advances in the field of epigenetics have shown that human cancer cells harbor global epigenetic abnormalities, in addition to numerous genetic alterations (3,4). These genetic and epigenetic alterations interact at all stages of cancer development, working together to promote cancer progression (5). The genetic origin of cancer is widely accepted however, recent studies suggest that epigenetic alterations may be the key initiating events in some forms of cancer (6). These findings have led to a global initiative to understand the role of epigenetics in the initiation and propagation of cancer (7). The fact that epigenetic aberrations, unlike genetic mutations, are potentially reversible and can be restored to their normal state by epigenetic therapy makes such initiatives promising and therapeutically relevant (8).

In this review, we take a comprehensive look at the current understanding of the epigenetic mechanisms at work in normal mammalian cells and their comparative aberrations that occur during carcinogenesis. We also discuss the idea of cancer stem cells as the originators of cancer and the prospect of epigenetic therapy in designing efficient strategies for cancer treatment.

Massive cancer genome study reveals how DNA errors drive tumor growth

The largest ever study to analyze entire tumor genomes has provided the most complete picture yet of how DNA glitches drive tumor cell growth. Researchers say the results, released today in six papers in Nature and 17 in other journals, could pave the way for full genome sequencing of all patients’ tumors. Such sequences could then be used in efforts to match each patient to a molecular treatment.

The Pan-Cancer Analysis of Whole Genomes (PCAWG) project, which had a cast of more than 1300 scientists and clinicians around the world, analyzed 2658 whole genomes for 38 types of cancer, from breast to liver. “What stands out from these studies is the rigor of doing this in a systemic way,” says cancer geneticist Marcin Cieslik, who with colleague Arul Chinnaiyan at the University of Michigan, Ann Arbor, co-authored a commentary on the papers.

Previous published studies—such as those from the U.S.-funded Cancer Genome Atlas (TCGA)—originally looked only at the “exome,” protein-coding DNA that make up just 1% of the genome, of tumors because it was cheaper and easier. But this shortcut left out many changes that might drive cancer growth. With DNA sequencing costs falling, the TCGA and the International Cancer Genome Consortium turned to the entire genome about 10 years ago, sequencing all 3 billion DNA base pairs, including regulatory regions within noncoding DNA, for many tumor samples. These groups also looked for large rearrangements and other structural changes that exome sequencing misses.

The PCAWG study’s 1300-strong team then dug into the data, which the other groups had made freely available in databases. Its analysis didn’t find many new so-called “driver” mutations within genes or noncoding DNA that power cell growth in tumors. But the researchers found “many more ways … to change those pathways” of cancer growth, said project member Lincoln Stein of the Ontario Institute for Cancer Research during a press call. For example, about one-fifth of the tumors had cells in which chromosomes shattered and rearranged, a bizarre phenomenon known as chromothripsis.

Each tumor had four to five driver mutations on average. In all, the PCAWG project was able to find at least one driver mutation in about 95% of the tumor samples, compared with just 67% with exome sequencing, says Peter Campbell of the Wellcome Sanger Institute, another project member. This means many more cancer patients can in principle now be matched to a drug that targets the protein made by that driver gene.

One PCAWG team also figured out how to trace the evolution of the mutations in a single tumor biopsy. The group confirmed that the initial mutations often cropped up years or decades before the cancers were diagnosed, suggesting many could be detected and treated much earlier. Another team found new patterns of mutations that result from environmental exposures such as tobacco smoke. The papers in other journals explore topics such as how often tumor genomes contain DNA from viruses that may have triggered the cancer (13% of the samples).

Some countries, such as the United Kingdom, are moving toward whole-genome sequencing of every cancer patient’s tumor to guide treatment the full cost is still thousands of dollars per genome, Campbell says. The PCAWG analysis could be “a blueprint for these national programs,” he says. The PCAWG consortium has also begun to pool clinical records and genomes for 100,000 patients to create a “knowledge bank” that doctors could consult to determine the best treatment based on a patient’s tumor genome.

Cieslik and Chinnaiyan note that most of the same information could be gleaned by combining exome data with cheaper tests such as RNA sequencing and assays for rearrangements. “Whether whole-genome sequencing is ultimately the best method in the clinic remains to be seen,” Cieslik says. But the wealth of data from the PCAWG study, which is now freely available to researchers, will help biologists understand the mechanisms of cancer, they say.

Another caveat is that although targeted drugs can be less toxic and more powerful than chemotherapy, most patients’ tumors grow back as a few cells that resist the drug begin to expand. The patient may then need another drug to kill the resistant cells. “It’s certainly true that this kind of sequencing will not mean that all cancers are cured,” Campbell says. “But it points us to where we should be thinking about developing drugs for preventing resistance or treating it once it arises.”

Cancer Biology

The Cancer Biology portion of the site contains in-depth information about the structure and function of normal cells and cancer cells. The changes that make normal cells turn into cancer cells are described. Topics covered include:

Biological Building Blocks - Information on the molecules that are found in living things. Includes proteins, carbohydrates, lipids and nucleic acids.

Cell Structure - Discusses the functional parts of cells called organelles. Organelles covered include the nucleus , ribosomes, mitochondria and the cytoskeleton

The Cell Cycle - A look at the clock-like flow that cells go through when they are growing and dividing.

Cell Division - Covers the control of normal cell division and the defects seen in cancer cells.

Gene Function - Discusses the way genetic information is used in cells.

Mutation - Describes the types and causes of changes to genes (mutations) that can result in cancer.

Cancer Genes - Describes the types of genes (oncogenes and tumor suppressors) that are altered in cancer. Some key examples are given for each type of gene. Contains a section on microRNAs (miRNAs) and their role in cancer.

Cancer Epigenetics - Changes in DNA can be subtle, but have huge impacts on the way cells behave. Epigenetics is the study of these small-but-important changes.

Causes of Cancer - Includes details about the causes of cancer, including chemicals, radiation and viruses

Cancer Development - Cancer progresses in a stepwise manner, often taking years to become detectable. Learn about that process here.

Cancer Metabolism - All cells need energy and oxygen to survive. Cancer cells need a lot of energy to reproduce. Often, cancer cells don't get their energy the same way normal cells do, and this can impact their growth and their response to cancer treatments.

Cancer Cell Death ( Apoptosis ) - Most cancer drugs are designed to kill cancer cells. The death of cancer cells is a key step in stopping growth, and it happens in a very orderly-fashion.

Angiogenesis - Animations and text describe how tumors develop a blood supply. Includes discussions of drugs that fight cancer by blocking this critical process.

Metastasis - The majority of cancer deaths are caused by spread of the disease from its orginal location. This section covers the 'how' and 'why' of cancer spread. Also covered are attempts to interefere with the process in cancer patients.

Tumor-Host Interactions - There are many interactions between different cells in a tumor. This section covers some of the key cell types and the ways that they influence the growth of a tumor.

Microbiome - We are covered with (and full of) tiny organisms that influence our health for the better or worse. Learn about how these bacteria influence cancer growth and treatment responses.

The Immune System - The immune system is involved in guarding our bodies from internal and external threats, including cancer. Because of the important role of immune cells in preventing and possibly contributing to cancer, as well as the use of immune cells and products in treating cancer, the subject is treated here in detail.

Cancer in Domesicated Animals and Pets - Animals other than humans get cancer and this section examines a few types of cancer in dogs and cats.

Cancer in Wild Animals - For millions of years, wild animals have been getting cancer, including some strange ones that get spread when animals bite each other or mate.