Different Cancers Can Share Genetic Signatures

Posted on October 22nd, 2013 by Dr. Francis Collins

Cancer is a disease of the genome. It arises when genes involved in promoting or suppressing cell growth sustain mutations that disturb the normal stop and go signals.  There are more than 100 different types of cancer, most of which derive their names and current treatment based on their tissue of origin—breast, colon, or brain, for example. But because of advances in DNA sequencing and analysis, that soon may be about to change.

Using data generated through The Cancer Genome Atlas, NIH-funded researchers recently compared the genomic fingerprints of tumor samples from nearly 3,300 patients with 12 types of cancer: acute myeloid leukemia, bladder, brain (glioblastoma multiforme), breast, colon, endometrial, head and neck, kidney, lung (adenocarcinoma and squamous cell carcinoma), ovarian, and rectal. Confirming but greatly extending what smaller studies have shown, the researchers discovered that even when cancers originate from vastly different tissues, they can show similar features at the DNA level

In fact, the new analysis, just published in the journal Nature [1], lists 127 significantly mutated genes that are shared by subsets of samples across the 12 cancer types. Many of these mutated genes are notorious culprits that can initiate cancer’s uncontrolled growth or drive its progression. But others are relatively new suspects in the cancer line-up. These include genes that regulate the activity of other genes, that control the disposal of proteins, and that modify how DNA wraps around histones, which are spool-like proteins that provide structural support to chromosomes.

What is most exciting here is the potential to identify key genomic changes shared by certain subsets of tumors, regardless of where they arise in the body. Such information is vital to our efforts to develop more individualized approaches for helping people with cancer—called personalized medicine, or precision medicine. For example, if a patient’s tumor has a genomic fingerprint that indicates it is likely to spread to other areas of the body, or metastasize, doctors may suggest a more aggressive treatment strategy than they would for someone whose tumor had a different profile.

Genomic information might also help us figure out if a drug originally approved for use in one type of cancer might be useful in treating other types. For example, if a drug works for colon cancer, it might also work for a lung cancer with a similar genetic fingerprint.

In addition to enabling doctors to use today’s cancer treatments in a more precise manner, genome-based research is laying the foundation for tomorrow’s cancer therapies. The wealth of genetic data generated by The Cancer Genome Atlas is accelerating efforts to identify key cellular pathways involved in cancer and to determine which are prime targets for therapeutic development.

This study, along with several other studies published this month’s issue of Nature Genetics [2–5], are just some of the roughly 20 papers that the NIH-supported “Pan-Cancer project” expects to publish in coming months. But, based on these exciting early findings, I look forward to a time in the not-too-distant future when cancer patients will receive treatments based on their tumor’s genomic signature—treatments that we all hope will be more effective and less toxic than the traditional chemotherapy approach to medicine.

References:

[1] Mutational landscape and significance across 12 major cancer types. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L. Nature. 2013 Oct 17;502(7471):333-9.

[2] Emerging landscape of oncogenic signatures across human cancers. Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. Nat Genet. 2013 Oct;45(10):1127-1133.

[3] Pan-cancer patterns of somatic copy number alteration. Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhang CZ, Wala J, Mermel CH, Sougnez C, Gabriel SB, Hernandez B, Shen H, Laird PW, Getz G, Meyerson M, Beroukhim R. Nat Genet. 2013 Oct;45(10):1134-1140.

[4] The Cancer Genome Atlas Pan-Cancer analysis project. Cancer Genome Atlas Research Network; Genome Characterization Center, Chang K et al. Nat Genet. 2013 Oct;45(10):1113-20.

[5] Enabling transparent and collaborative computational analysis of 12 tumor types within The Cancer Genome Atlas. Omberg L, Ellrott K, Yuan Y, Kandoth C, Wong C, Kellen MR, Friend SH, Stuart J, Liang H, Margolin AA. Nat Genet. 2013 Oct;45(10):1121-6.

Link:

The Cancer Genome Atlas

NIH support: National Cancer Institute; National Human Genome Research Institute