Intratumor heterogeneity seen in renal carcinomas

March 8, 2012
Intratumor heterogeneity seen in renal carcinomas

(HealthDay) -- Extensive intratumor heterogeneity, seen in samples obtained from renal carcinomas, may lead to underestimation of the tumor genomics based on single tumor-biopsy samples, according to a study published in the March 8 issue of the New England Journal of Medicine.

To investigate intratumor heterogeneity, Marco Gerlinger, M.D., from the Cancer Research U.K. London Research Institute, and colleagues performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples from primary renal carcinomas and associated metastatic sites. The consequences of this heterogeneity were characterized using immunohistochemical analysis, mutation functional analysis, and expression profiling.

The researchers found that phylogenetic reconstruction showed branched evolutionary tumor growth; and across every tumor region, 63 to 69 percent of were not detectable. Intratumor heterogeneity was seen for a mutation within an autoinhibitory domain of the mammalian target of rapamycin kinase, and mutational heterogeneity was observed for multiple tumor-suppressor genes converging on loss of function. In different regions of the same tumor, gene-expression signatures of good and were seen. Extensive intratumor heterogeneity was seen on allelic composition and ploidy profiling analysis.

"Intratumor heterogeneity may explain the difficulties encountered in the validation of oncology biomarkers owing to sampling bias, contribute to Darwinian selection of preexisting drug-resistant clones, and predict therapeutic resistance," the authors write. "Reconstructing tumor clonal architectures and the identification of common mutations located in the trunk of the phylogenetic tree may contribute to more robust biomarkers and therapeutic approaches."

The study was partially funded by Novartis; several authors disclosed with pharmaceutical companies, including Novartis.

Explore further: Epigenetic study reveals new insights into breast cancer

More information: Full Text (subscription or payment may be required)
Editorial (subscription or payment may be required)

Related Stories

Single-cell sequencing leads to a new era of cancer research

March 2, 2012

BGI, the world's largest genomics organization, developed single-cell genome sequencing technology and published two research papers for cancer single-cell sequencing in the research journal Cell. In the papers, which were ...

Recommended for you

Elephants provide big clue in fight against cancer

October 9, 2015

Carlo Maley spends his time pondering pachyderms—and cactuses and whales, and a wide array of non-human species—all in pursuit of the answer to this question: Why do some life forms get cancer while others do not?

Compound doubles up on cancer detection

October 8, 2015

Tagging a pair of markers found almost exclusively on a common brain cancer yields a cancer signal that is both more obvious and more specific to cancer, according to a study published last week in the Proceedings of the ...


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.