Abstract 2396: Heterogeneity of colorectal cancers and multiple liver metastases by mutation and copy number profiling

Abstract

Abstract To investigate genetic and genomic heterogeneity in liver metastases of colorectal cancer, multiple tumor foci in the liver per patient were identified on the basis of radiological images and samples from these systematically biobanked. For a total of 67 patients, 258 metastatic tumor samples were collected (minimum of 2 and maximum of 9 samples per patient, median of 4 samples per patient). Additionally, for n = 14 patients, tumor samples from the corresponding primary colorectal cancer were also available. DNA isolated from these samples was subjected to mutation profiling by Sanger sequencing for the genes BRAF, KRAS, PIK3CA and TP53, as well as allele-specific copy number profiling by CytoscanHD SNP array. For the four genes investigated for mutations, 39/67 (58%) of the patients were homogeneous in their mutation profile, while 21/67 (32%) were heterogeneous (one or more samples had mutations not detected in all samples). For 7/67 patients (10%), no mutations were detected in any of these four genes. For 9/14 patients with matching primary tumors, there was complete concordance between the primary tumor and all liver metastases profiled for mutations, while the remaining 5/14 patients showed discordance in mutation profile between the primary tumor and at least one of the liver metastases profiled. High resolution copy number profiles of this cohort detected many of the aberrations previously described in primary colorectal cancer, specifically gain of chromosomes 7, 8q, 13q and 20q, and loss of chromosomes 5q, 8p, 15q, 17p and 18q. The extent of heterogeneity observed in patient-wise mutation profiles was largely mirrored in the copy number profiles of the same tumors. 16/27 (60%) of the patients for which both mutation and copy number profiles were available showed concordance in the degree of heterogeneity per patient. In summary, intra-individual heterogeneity varied from patient to patient, with results from the genetic and genomic data types largely concurring. Citation Format: Sharmini Alagaratnam, Tuva Høst Brunsell, Stine Aske Danielsen, Anita Sveen, Mette Eknæs, Merete Hektoen, Bård Røsok, Bjørn Atle Bjørnbeth, Arild Nesbakken, Ragnhild Lothe. Heterogeneity of colorectal cancers and multiple liver metastases by mutation and copy number profiling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2396.