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Different Cancers, Same Mutations

Scientists document common genetic alterations in cancers of different origins.

By | September 26, 2013

STOCK.XCHNG SCHULERGDAn astounding variety of genetic abnormalities can cause healthy cells to turn cancerous. Few of these are shared among cancers of the same tissue, and fewer still are shared among cancers of different tissues. Nevertheless, scientists searching for such common genetic needles in an array of cancer haystacks document their findings in two papers published today (September 26) in Nature Genetics.

“For the first time we have been able to analyze, across the board, large numbers of tumor samples . . . and also systematically look across different tumor types,” said Chris Sander, chair of the computational biology program at the Memorial Sloan-Kettering Cancer Center in New York, and senior author on one of the new papers. The aim, he said, was to learn about principles of cancer biology that might not have been obvious from previous studies examining one tumor type in isolation.

The work of Sander and his colleagues, together with a study led by Rameen Beroukhim, a professor of medicine at Harvard Medical School in Cambridge, Massachusetts, are the first two research papers in a series of pan-cancer analyses to be published by contributors to The Cancer Genome Atlas (TCGA).

“TCGA is all about analyzing each tumor type separately,” said Josh Stuart, a professor of biomolecular engineering at the University of California, Santa Cruz, who was not involved in either study. “[But] every time we did the next cancer, we always wanted to compare it to the previous one we’d analyzed because we would recognize some similarities,” he said. The Pan-Cancer Analyses Working Group of TCGA, which is coordinated by Stuart, was thus born.

One benefit of looking at cancer samples from all tissue types is that the pool of data becomes larger, offering more statistical power, Stuart explained. For example, Beroukhim and his colleagues were able to look at a staggering 4,934 samples from 11 different cancer types. Sander’s team, meanwhile, examined 3,299 samples from 12 cancer types.

Beroukhim’s team examined DNA copy number alterations—common features in cancer—at roughly 1.5 million loci across the genome. They found approximately 200,000 copy number alterations in total, which worked out to about 39 alterations per cancer sample.

To determine which of these alterations might be causing cancer, the researchers looked for only those that recurred across various cancer types. By doing so, they whittled down the 200,000 or so loci to just 140. Only 35 of these loci contained known oncogenes or tumor suppressor genes, meaning the remaining 105 contained new cancer-causing candidates to investigate.

Sander’s team—which studied gene mutations and DNA methylation changes in addition to copy number alterations—similarly whittled down many thousands of such genetic aberrations to just 479 that were recurrent across multiple cancer types.

The team then asked which of these 479 genetic events occurred in each cancer sample, paving the way for new categories of cancer based on the particular constellations of aberrations they possessed. Interestingly, the team found that cancers with abundant single gene mutations tended not to have many copy number alterations and vice versa.

“What both groups come to in conclusion is that we have a spectrum of tumors that are driven by copy number abnormalities . . . and then another set of tumors that are driven primarily by a series of mutational events,” said Gordon Mills, chair of systems biology at the University of Texas MD Anderson Cancer Center, who was not involved in the work. “The two papers provide . . . a very cogent argument that these are two of the major driving events,” he said.

Beyond learning more about the mechanisms behind the disease’s origins, said Sander, such pan-cancer studies “might lead to a new kind of clinical trial.” Sander described such studies as basket or matrix trials, in which patients with different tumor types—for example, breast, ovarian, or colorectal—but similar constellations of genetic alterations, would be treated with the same drug or drugs.

Of course, Mills stressed, tissue type is still important. It’s possible that the same mutation in different cancer types could indicate different responses to drugs. “There is an opportunity and even a need for basket trials,” he said, “but while this is extremely attractive, it is clearly a hypothesis that is going to require extensive testing.”

G. Ciriello et al., “Emerging landscape of oncogenic signatures across human cancers,” Nature Genetics, doi:10.1038/ng.2762, 2013.

T. I. Zack et al., “Pan-cancer patterns of somatic copy number alteration,” Nature Genetics, doi:10.1038/ng.2760, 2013.

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Avatar of: Kathy3

Kathy3

Posts: 1

September 27, 2013

My family has Lynch Syndrome. A genetic mutation that involves a handful of cancers. At 36 I was dx with stage3 colon cancer , my mother was 36 & 66 when she had colon cancer, her brother had colon and prostate cancer. My youngest brother had 75% of his colon removed at 41, and my youngest child was dx with glioblastoma at 10 yrs old, total resection, radiation n chemo, then it returned a year later, another resection n 3 years of chemo, he is now just shy of 21, super intelligent, shooting for med school. I like the fact there is research continuing on genetic mutation genes. One day I pray there is a cure.

Avatar of: Transcriptase

Transcriptase

Posts: 1

September 28, 2013

Sorry to hear what you and your family had to go through. :(

 

However, research is extremely promising, with the advent of newer imaging and detection methods, as well as development of more precise delivery mechanisms for drugs.

 

While it is unlikely that there will be a "magic bullet" to fix all cancers, due to the diverse nature of the mutations that cause them, accumulation of various treatment methods are piling up.

Avatar of: Sergio Stagnaro

Sergio Stagnaro

Posts: 3

September 28, 2013

Unfortunately, overlooking mit-DNA,  almost all Physicians around the world are wrongly thinking that analyzing exclusively n-DNA, it could be possible to understand the onset of a cancer. For instance, "Beroukhim’s team examined DNA copy-number alterations ....", but, beside n-DNA it exists also mit-DNA!  In addition, none thought that gene mutation  must bribg about  biological function alteration to be important (Stagnaro Sergio. Biological System Functional Modification parallels Gene Mutation. www.Nature.com, March 13, 2008,http://blogs.nature.com/nm/spoonful/2008/03/gout_gene.html ). Now we are able to bed-side evaluate every biological function by means of Quantum Biophysical Semeiotics. Finally, all serious disorders, including CVD, T2DM and Cancer, involve indivilduals with a singular mitochondrial cytopathy, I termed 33 years ago Congenital Acidosic Enzyme-Metabolic Histangiopathy (CAEM), conditio sine qua non of a flurry of pathologial conditions, bed-side diagnosed from birth, and removed by Quantum Therapy: Sergio Stagnaro and Simone Caramel (2013). The Role of Modified Mediterranean Diet and Quantum Therapy in Oncological Primary Prevention.  Bentham PG., Current Nutrition & Food Science  ISSN (Print): 1573-4013;  ISSN (Online): 2212-3881. VOLUME: 9,  ISSUE: 1; DOI: 10.2174/1573401311309010011;  http://www.benthamscience.com/contents-JCode-CNF-Vol-00000009-Iss-00000001.htm; Sergio Stagnaro and Simone Caramel (2013). The Inherited Real Risk of Coronary Artery Disease, Nature PG., European Journal of Clinical Nutrition, 67, 683 (June 2013) | doi:10.1038/ejcn.2013.37, http://www.nature.com/ejcn/journal/v67/n6/full/ejcn201337a.html [MEDLINE] ; Sergio Stagnaro and Simone Caramel.  BRCA-1 and BRCA-2 mutation bedside detection and breast cancer clinical primary prevention.  Front. Genet. | doi: 10.3389/fgene.2013.00039.  http://www.frontiersin.org/Cancer_Genetics/10.3389/fgene.2013.00039/full  [MEDLINE]; Sergio Stagnaro and Simone Caramel (2013).    Inherited Real Risk of Type 2 Diabetes Mellitus: bedside diagnosis, pathophysiology and primary prevention. Frontiers in Endocrinology. Front Endocrinol (Lausanne). 2013; 4: 17. Published online 2013 February 26. doi:  10.3389/fendo.2013.00017; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581808/  [Pub-Med indexed for MEDLINE] .

September 30, 2013

I too have Lynch Syndrome. I was diagnosed last year after they found colon cancer during a colonoscopy meant to looks for signs of Chron's disease.They did the genetic testing because colon cancer in a 27 year old is almost unheard of. It hasn't come back yet, but they said my chances of it coming back within 5 years is 80%, and that my 10 year prognosis is 10-20%. From the perspective of a Lynch Syndrome patient, this hardly seems like news.
Avatar of: Ferromagnetism

Ferromagnetism

Posts: 4

November 13, 2013

Scientists identify genetic errors in 12 major cancer types. All cancers are characterized by extensive genomic instability, which can be detected among all histological subtypes and among different foci within a tumor. Unfortunately, it is now widely accepted that cancer is a genetic disease and that alterations in the DNA sequence underlie the development of every cancerous tumor. On the one hand, inherited abnormal iron metabolism in various organs can cause inherited forms of cancer, and on the other hand, sporadic iron events can cause sporadic forms of cancer. Numerous laboratory and clinical investigations over the past few decades have observed that in both animals and humans, primary tumors develop at body sites of excessive iron deposits. Excess iron in various organs and iron homeostasis-related genes cause sporadic and inherited forms of cancer. According to the Ferromagnetic Cancer Theory (Theory from The OLD TESTAMENT; Iron Conception), ancient accurate anti-iron cancer treatment methods can beat any cancer. Ceramic needles can suppress any tumors and large metastases. Ceramic needles can create harmless infiltrations (harmless necroses; deposits of cells that die; benign capsules). Ceramic needles can enter anti-iron solution [sulfur (2%) + olive oil (98%); 36.6C - 39.0C] to tumors and large metastases. Anti-iron slow blood loss (even 75%) [hemoglobin control], anti-iron goat milk diet and anti-iron drinking water containing hydrogen sulfide can neutralize any micrometastases and isolated tumor cells.  http://www.medicalnewstoday.com/releases/267552.php  ;  http://www.medicalnewstoday.com/opinions/103745/  ;  http://www.medicalnewstoday.com/opinions/122203/  ;  http://healthland.time.com/2011/07/13/almost-every-type-of-cancer-kills-more-men-than-women-study-shows/  ;  http://www.the-scientist.com/?articles.view/articleNo/37661/title/Different-Cancers--Same-Mutations/  ;  Together We (The Scientist, Medical News Today, TIME and Vadim Shapoval) Will Beat CANCER

Avatar of: Ferromagnetism

Ferromagnetism

Posts: 4

November 28, 2013

Father of Oncology, Ferromagnetic Cancer Theory, US Thermonuclear Sun-2018 and Chinese Lunar Robots. The origin of the word CANCER is credited to the Greek physician Hippocrates (460-370 BC), who is considered the Father of Medicine. Rudolf Virchow, also known as the Father of Pathology, stated that no man, even under torture, can say exactly what a tumor is. Vadim Shapoval (born August 11, 1969), also known as the Father of Oncology, as the Father of the Thermonuclear Sun-2018, states that cells obey the same laws of chemistry and physics that determine the behavior of nonliving systems. Cancer is a disease of cells. Any human cell is composed of water; diamagnetic, paramagnetic, superparamagnetic, ferrimagnetic and ferromagnetic nanoparticles. Intracellular molecules FeO;Fe2O3;Fe3O4 are the main creators of intracellular superparamagnetic, ferrimagnetic and ferromagnetic nanoparticles. These nanoparticles can magnetically cause point genetic changes, chromosomal aberrations and chromothripsis within tumor cells. Tumor cells are riddled with genetic errors. The body has no natural way to rid itself of the excess iron. Any cancer is caused by iron-related genes (genes involved in iron metabolism) and iron-related events (when excess iron accumulates in the cells, tissues, and organs due to various causes). Any cancer is a subtle iron disease; intracellular superpara-ferri-ferromagnetic infection; death's firstborn who devours limbs (Job 18:13). According to the Ferromagnetic Cancer Theory (Theory from The Old Testament; Iron Conception), ancient accurate anti-iron methods can beat any cancer. After Stalin died in 1953, the TOKAMAK was developed in the mid-1960s by Soviet plasma physicists. TOKAMAK is Soviet Scientific Fraud. STELLARATOR is a device used to confine hot plasma with magnetic fields. Tokamaks and Stellarators must die. Chinese physicists should know American thermonuclear technologies. Petroleum and wheeled vehicles will die soon. US will create the Greatest Source of Electricity. US Nuclear Artillery will initiate the work of US Thermonuclear Sun-2018 in granite quarry. A star is a massive sphere of plasma held together by its own gravity. A star's life begins with the gravitational collapse of a gaseous nebula of material composed primarily of hydrogen, along with helium and trace amounts of heavier elements. Life of US Thermonuclear Sun will begin with the non-gravitational collapse of thermonuclear fuel (tritium, deuterium, lithium deuteride and LUNAR helium-3). Special artillery (numerous guns) will create (towards each other) non-gravitational collapse and will deliver thermonuclear fuel to the Thermonuclear Sun. It has been estimated that there are around 1100000 metric tons of helium-3 on the surface of the Moon down to a depth of a few meters. Russia, India, Japan and Germany are taking an interest in lunar exploration linked to helium-3 as a potential thermonuclear fuel. Chinese lunar robots must go to the Moon to mine helium-3 for US Thermonuclear Sun-2018.  http://www.medicalnewstoday.com/opinions/166358  ;  http://www.merriam-webster.com/dictionary/thermonuclear  ;  http://www.the-scientist.com/?articles.view/articleNo/37661/title/Different-Cancers--Same-Mutations/  ;  Together We (The Scientist, Medical News Today, TIME, Merriam-Webster and Vadim Shapoval) Will Beat CANCER

Avatar of: Ferromagnetism

Ferromagnetism

Posts: 4

December 19, 2013

Chinese Thermonuclear Sun and Ferromagnetic Cancer Theory. Ensuring a clean and plentiful supply of energy is one of the greatest challenges facing humanity. Efficient plasma confinement is the main challenge that has to be solved on the way towards thermonuclear suns that will work like miniature stars on Earth. US Thermonuclear Sun-2018 (the Greatest Source of Electricity) will beat petroleum, wheeled vehicles, power stations, stellarators, tokamaks and ITER (the world's largest tokamak); will destroy thermonuclear-research-money. Stellarators and tokamaks are failed devices. Magnetic fields cannot confine hot plasma because magnetic fields are polar fields with a North and South polarity; gravitational fields have no polarity at all. The gravitational forces in the stars compress matter, mostly hydrogen, up to very large densities and temperatures at the star-centers. US Thermonuclear Sun-2018 will eat thermonuclear fuel by special artillery (special guns will shoot synchronously, towards each other). Special artillery will compress sun-center; will deliver LUNAR helium-3, deuterium, tritium and lithium deuteride to sun-center. The People's Republic of China has landed its first robotic lander on the Moon. Chinese Lunar Robots will extract lunar helium-3. The People's Republic of China can create Chinese Thermonuclear Sun within Chinese granite quarry. Chinese nuclear artillery will initiate the work of Chinese Thermonuclear Sun. The creation of special artillery is the most difficult problem-2014-2018. Special artillery must work instead of the gravitational field of star. Cancer is now the leading cause of death in the People's Republic of China. Chinese scientists ignored and ignore (2013-2006=7) molecular biological, genetic and clinical aspects of the Ferromagnetic Cancer Theory (Theory from The Old Testament; Iron Conception). Was the Cultural Revolution good or bad? Ferromagnetic Cancer Theory will beat cancer; will destroy cancer-research-money. Any cancer is caused by iron-related genes (genes involved in iron metabolism / hereditary cancers) and iron-related events (when excess iron accumulates in the cells, tissues, and organs due to various causes / sporadic cancers). Any cancer is a subtle iron disease. There is an epidemic of cancer today. Most people continue to view cancer as a form of genetic lottery. In reality, cancer is a form of iron lottery. Ceramic needles can suppress any tumors and large metastases; can enter anti-iron solution [sulfur (2%) + olive oil (98%); 36.6C - 39.0C] to tumors and large metastases. Anti-iron slow blood loss (even 75%) [hemoglobin control], anti-iron goat milk diet and anti-iron drinking water containing hydrogen sulfide can neutralize any micro-metastases and isolated tumor cells.  http://www.merriam-webster.com/dictionary/thermonuclear  ;  https://plus.google.com/107119198688120551734/posts  ;  http://www.the-scientist.com/?articles.view/articleNo/37661/title/Different-Cancers--Same-Mutations/  ;  http://voices.yahoo.com/cancer-theories-explanations-1746827.html?cat=70  ;  http://healthland.time.com/2011/07/13/almost-every-type-of-cancer-kills-more-men-than-women-study-shows/  ;  http://www.weather.com/news/science/sun-and-thermonuclear-explosion-how-theyre-alike-20131016  ;  Vadim Shapoval

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