Oncogenic signatures mapped in TCGA a guide for the development of personalized therapy

September 27, 2013, Memorial Sloan-Kettering Cancer Center

Clinical trial design for new cancer therapies has historically been focused on the tissue of origin of a tumor, but a paper from researchers at Memorial Sloan-Kettering Cancer Center published on September 26 in Nature Genetics supports a new approach: one based on the genomic signature of a tumor rather than the tissue of origin in the body.

It is well known that the emergence of is a multi-step process, but because of the efforts of The Cancer Genome Atlas (TCGA), funded by the US National Institutes of Health, and other large-scale cancer genomics efforts, for the first time this process can be viewed in exquisite molecular detail, mapping mutations and other molecular events affecting any of the 20,000 genes in a human cell.

Now, two major hypotheses have been confirmed from the of more than 3000 samples from 12 different tumor types: a limited number of specific genetic events appear to cause most tumor subtypes and tumors can be grouped by the oncogenic signatures they contain, no matter what the tissue of origin. That these oncogenic signatures are largely independent of the particular tissue in which the cancer arises indicates that certain may be beneficial for select patients with different .

"In future clinical trials, we envision that patients with a certain type of endometrial cancer, for example, may be enrolled in the same trial as patients with a subtype of colorectal cancer, and that patient selection for clinical trials can be guided by cancer genomics profiling in the clinic," stated Chris Sander, one of the of Memorial Sloan-Kettering's Genome Data Analysis Center. "This work is intended to help in the design of such trials and the development of more-personalized cancer therapies."

The ability to reveal sets of cancer-causing events in molecular detail is based on three major technical and scientific developments in the last decade. New high-throughput genomic technologies and lower operating costs have enabled the collection of genetic data from many thousands of tumors. The experience and knowledge accumulated in cancer genomics in many laboratories has taught us which of the many molecular alterations in cancer are likely to contribute to oncogenesis. Linking data and knowledge, new algorithms and methods for large data analysis in the field of computational biology provide the ability to find the proverbial needles in the haystack: to derive cancer-causing molecular genetic signatures and link them to tumor subtypes and potential therapies on the background of extremely high levels of informational noise.

The Memorial Sloan-Kettering team and their colleagues in TCGA and the International Cancer Genome Consortium plan to expand these comprehensive analyses to tens of thousands of tumor samples. A glimpse of the molecular tumor landscape in more than 13,000 tumor samples is already accessible in the cBioPortal for Cancer Genomics at http://www.cbioportal.org.

Principal authors on the study are Giovanni Ciriello, Nikolaus Schultz, and Chris Sander of the Computational Biology Center at Memorial Sloan-Kettering.

Explore further: Most popular ovarian cancer cell lines do not resemble ovarian cancer

Related Stories

Most popular ovarian cancer cell lines do not resemble ovarian cancer

July 15, 2013
(Medical Xpress)—Researchers from Memorial Sloan-Kettering Cancer Center recently discovered that the most frequently used cancer cell lines in ovarian cancer research are not suitable models of ovarian cancer. Their findings ...

Testing for mutations identified in squamous cell lung cancer tumors helps personalize treatment

May 17, 2012
Screening lung cancer tumor samples for cancer-causing, or "driver," genetic mutations can help physicians tailor patients' treatments to target those specific mutations. While scientists have identified cancer-causing mutations ...

Pan-cancer studies find common patterns shared by different tumor types

September 26, 2013
Cancer encompasses a complex group of diseases traditionally defined by where in the body it originates, as in lung cancer or colon cancer. This framework for studying and treating cancer has made sense for generations, but ...

Enhanced luminal breast tumor response to antiestrogen therapy

September 3, 2013
Breast cancer can be divided into 4 major subtypes using molecular and genetic information from the tumors. Each subtype is associated with different prognosis and should be taken into consideration when making treatment ...

Genomics to reshape endometrial cancer treatment

May 1, 2013
The most in-depth look yet at endometrial cancer shows that adding genomics-based testing to the standard diagnostic workup could change the recommended course of treatment for some women.

'Wildly heterogeneous genes'

September 15, 2013
Cancer tumors almost never share the exact same genetic mutations, a fact that has confounded scientific efforts to better categorize cancer types and develop more targeted, effective treatments.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.