Rare genetic heterogeneity within single tumor discovered for the first time in colorectal liver metastases after liver resection

Oncotarget
Mylène SebaghA Lemoine

Abstract

Effective individualized treatment of patients with colorectal liver metastases (CLM) requires tumor genotyping, usually based on the analysis of one single sample per patient. Therapy failure may partially be explained by sampling errors and/or intratumoral genetic heterogeneity. We aimed to demonstrate intratumoral genetic heterogeneity in CLM and enable pathologists to select tumor tissue for genotyping. All the tumors of 86 patients who underwent liver resection for a single CLM were reviewed. Of the 86 patients, 66 patients received chemotherapy and 20 patients did not receive chemotherapy before liver resection. All the tumor areas sampled were analyzed for KRAS, BRAF, PIK3CA, and NRAS mutations. The mutational status was tested in 74 cases, 7 cases had no tumoral cells due to complete responses and 5 blocks were unavailable. Of the 59/74 CLM with > 1 sample, 56 showed the same mutational status between the samples. The remaining 3 cases (5% of all cases) showed genetic heterogeneity for KRAS in 2 and BRAF in 1 patient. Genetic heterogeneity correlated with lower rate of viable tumor cells (p=0.009) and higher rate of mucin pools (p=0.013). We demonstrate for the first time the existence of genetic intratumoral heterogene...Continue Reading

References

Aug 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marie-Christine Etienne-GrimaldiGérard Milano
Oct 22, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dan G BlazerJean-Nicolas Vauthey
Jan 28, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephan E BaldusHelmut E Gabbert
Jun 6, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Efsevia VakianiDavid B Solit
Dec 24, 2015·Journal of Gastrointestinal Oncology·Marla Lipsyc, Rona Yaeger

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Methods Mentioned

BETA
genotyping
biopsies
PCR
chip

Software Mentioned

pROC
R

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