Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable Left-sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival

摘要

Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC patients sequenced (n=401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification. In both the MSK-IMPACT and TCGA datasets, BCL2L1 was the most frequently amplified 20q oncogene. However, SRC was the only recognized 20q oncogene with a significant inverse relationship between mRNA upregulation and RAS/RAF mutation (OR: -0.4 +/- 0.2, p=0.02). In comparison to 20q diploid CRC, 20q gain/amplification was associated with wild-type (WT) KRAS (p<0.001) and BRAF (p=0.01), microsatellite stability (MSS) (p<0.001), distal primary tumors (p<0.001), and mutant TP53 (p<0.001), but not stage. On multi-variate analysis, longer overall survival from date of metastasis was observed with chromosome 20q gain (p=0.02) or amplification (p=0.04) compared to diploid 20q.