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Tumors More Heterogeneous Than Previously Recognized

TOP - April 2012, Vol 5, No 2 published on April 30, 2012

Researchers have documented diverse genetic changes in different parts of the same primary tumor, suggesting that individual tumors harbor a complexity of genetic changes that has not been well appreciated (Gerlinger M, Rowan AJ, Horswell S, et al. N Engl J Med. 2012;366:883-892). This discovery has implications for personalized medicine directed at genetic changes identified in 1 biopsy of a primary tumor. “Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor biopsy samples and may present challenges to personalized medicine and biomarker development,” wrote the authors. They noted that the extent of intratumoral heterogeneity is what was striking and surprising in this study.

The small study found more genetic differences than genetic similarities between biopsies taken from different parts of the same tumor. The authors also found differences in genetic changes between the primary tumor and local as well as distant metastases. The fact that the primary tumor has different genetic characteristics than metastases from that tumor has been documented in breast cancer, and there is currently a movement to recommend biopsies of metastases when they develop in addition to primary tumor biopsies.

The study analyzed cancer genomics in biopsy samples of a total of 30 biopsies from 4 primary tumors. Genomic analysis revealed that 26 of the 30 biopsies had different genetic expressions. The authors identified 118 different genetic mutations. About 40 were found in all the biopsies from the primary tumor and the metastases (ubiquitous mutations), and 53 mutations were shared. Twenty-five mutations were found only in a single biopsy (“private mutations”). Furthermore, gene expression signatures associated with a good prognosis and also those associated with a poor prognosis were seen in different sites of the same primary tumor.

Likening the genetic changes to a trunk and branches of a tree, the authors said that some genetic changes were seen early in the “trunk,” while others evolved over time into different “branches.” In an accompanying editorial, Dan Longo, MD, deputy editor of the New England Journal of Medicine, wrote that these observations suggest that it is probably “too simple” to direct therapy according to genetic tumor markers due to the heterogeneity observed within a single tumor.

Last modified: July 22, 2021