New TCGA Study Provides Molecular Classification Of 12 Cancer Types

The European Society for Medical Oncology (ESMO) has just announced the results of a study performed by researchers from The Cancer Genome Atlas (TCGA) Research Network. According to the ESMO, this study is the largest, most diverse tumor genetic analysis ever conducted, revealing a new approach to classifying cancers. The study offers a new perspective to how cancers are diagnosed and treated, and could also have a profound impact on future drug development.

In their recent work published in the journal Cell, the TCGA researchers compared over 3,500 specimens from 12 different cancer types, to create the largest data set of tumor genomics ever assembled. The genetic analysis of the tumors revealed that cancers are more likely to be genetically similar based on the type of cell in which the cancer originated, rather than the type of organ or tissue in which the cancer originated.

The TCGA was launched in 2006 with the goal of compiling genomic atlases of more than 20 types of cancer. As commonalities across cancer types began to emerge during the research,  the TCGA Pan-Cancer Initiative was launched in October 2012 to understand these correlations. A helpful review of their recent findings and implications for future therapies is provided in one of their news releases.

In this latest study, the TCGA researchers performed an integrative analysis using five genome-wide platforms and one proteomic platform. The analysis revealed that the tumors could be classified into 11 major tumor subtypes, of which five subtypes were nearly identical to their tissue-of-origin counterparts.

However, several distinct cancer types based on tissue-of-origin were found to converge into common subtypes. For example, bladder cancers split into three pan-cancer subtypes, one nearly identical to lung adenocarcinomas, and another most similar to squamous-cell cancers of the head and neck and of the lungs. These findings provide a clue as to why patients with bladder cancer often respond very differently when treated with the same systemic therapy.

Breast cancer is another example of the genetic differences within a single tissue type. The multiple types of cells in the complex breast organ give rise to multiple types of breast cancer. In this analysis, the researchers saw that the basal-like breast cancers have more in common with ovarian cancer and cancers of a squamous-cell type origin, rather than other types of breast cancers.

This new perspective of analyzing cancers according to their genomic profiles is a big shift away from the current norm of organizing cancer by organ or tissue of origin. Cancers that are described by their mutations, such as an ERBB2 amplified tumor or a PI3K-pathway mutant carcinoma, can offer a new approach to treatments. The TCGA researchers believe that this type of cross-cancer analysis will eventually help to tailor treatment strategies to subsets of patients, resulting in clinical trials that match individual patients to a drug or combination of therapies tailored to a tumor’s genetic profile.