UNASSIGNED: Synchronous @entity14 (sCRC) are clinically challenging @entity5 . Although the epidemiological characteristics are quite well established, their biological basis is still poorly understood. Hence, we performed comprehensive molecular profiling of 23 sCRC cases comprising 50 synchronous @entity5 , 5 metastases, and corresponding normal tissue by targeted deep sequencing of 30 CRC-related genes, microsatellite analysis and analysis for methylated @entity6756 . We identified a striking inter- and intratumoral genetic heterogeneity of sCRC. Twenty (87%) cases showed genetic heterogeneity leaving only three cases with @entity5 that had an identical genetic make-up. Intertumoral heterogeneity was frequently observed for clinically actionable genes, including @entity984 . Specifically, 44% of the cases @entity5 of which at least one was @entity984 mutated and the other @entity984 wildtype. Moreover, 48% of the cases had at least double, sometimes even triple or quadruple mutations in @entity984 , APC, @entity876 , @entity10160 , and @entity2534 , most of them being subclonal events. Lastly, we detected four cases (17%) with @entity5 with one case harboring one MSI- and a distinct microsatellite stable @entity189 . Our data demonstrate a striking genetic heterogeneity not only between different sCRC of a single case but also within a @entity5 . These results contribute to the biological understanding of sCRC and directly impact genotyping strategies and oncological decision making. Testing one @entity5 or a single metastasis may not suffice in the sCRC setting as clinically relevant and @entity5 -specific genetic information may be left undetected compromising optimal oncological therapy.    2015 Wiley Periodicals, Inc.

Genetic heterogeneity in synchronous XXXX impacts genotyping approaches and therapeutic strategies.

@entity6756 :: ('4292', 'Gene') :: ['MLH1'] @entity2534 :: ('7048', 'Gene') :: ['TGFBR2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'primary tumors', 'single tumor', 'microsatellite instable (MSI) tumors', 'harbored tumors', 'neoplasms', 'tumors'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinoma'] @entity876 :: ('7157', 'Gene') :: ['TP53'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal carcinomas'] @entity10160 :: ('5290', 'Gene') :: ['PIK3CA']
@entity14 :: (MESH:D015179,Disease) :: ['colorectal cancers']
