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

Abstract

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.

Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population

“…However, this result should be interpreted with caution since it was obtained for only two cell lines and has no statistical support. In CRC, the GNAS locus is frequently amplified which correlates with its increased mRNA expression (Ptashkin et al, 2017). Importantly, we previously observed a sig- Presence of 3C-Seq reads confirms the interaction of GNAS locus with rs6702619 region.…”

Multi-omics Approach Reveals Distinct Differences in Left- and Right-Sided Colon Cancer

“…6). More recently, Ptashkin and colleagues (48) find that chromosome 20q amplification is associated with a better OS in LCC. In addition, because cetuximab is mainly used in advanced stages of colorectal cancer patients, FMGS mining is further conducted in four pathologic stages according to the American Joint Committee on Cancer standards.…”

TTPAL Promotes Colorectal Tumorigenesis by Stabilizing TRIP6 to Activate Wnt/β-Catenin Signaling

“…Recent studies have suggested that genes with CNAs are potential biomarkers and/or therapeutic targets for colorectal cancer. Therefore, detection and mapping of copy number abnormalities provide an approach for associating aberrations with disease phenotype and for localizing critical genes (4,5). It is importance to identify and functionally characterize novel genes with CNAs that are associated with colorectal cancer (4).…”

“…Chromosome 20q amplification has been commonly found in colorectal cancer and is involved in transforming adenoma to carcinoma (5,6). Chromosome 20q amplification is also a potential indicator of poor prognosis in patients with colorectal cancer (7)(8)(9).…”