Abstract
Mucinous carcinoma (MC) is found in 10%-15% of colorectal cancer (CRC) patients. It differs from the common adenocarcinoma (AC) in histopathological appearance and clinical behavior. Genome-wide DNA copy number and survival data from MC and AC primary CRC samples from patients from two phase III trials (CAIRO and CAIRO2) was compared. Chromosomal copy number data from The Cancer Genome Atlas (TCGA) was used for validation. Altogether, 470 ACs were compared to 57 MCs. MC showed a reduced amount of copy number aberrations (CNAs) compared with AC for the CAIRO/CAIRO2 cohort, with a median amount of CNAs that was 1.5-fold lower (P = 0.002). Data from TCGA also showed a reduced amount of CNAs for MC. MC samples in both cohorts displayed less gain at chromosome 20q and less loss of chromosome 18p. A high rate of chromosomal instability was a strong negative prognostic marker for survival in MC patients from the CAIRO cohorts (hazard ratio 15.60, 95% CI 3.24-75.05). Results from this study indicate that the distinct MC phenotype is accompanied by a different genetic basis when compared with AC and show a strong association between the rate of chromosomal instability and survival in MC patients.
Highlights
Colorectal cancer (CRC) is categorized by histological subtype according to the WHO classification
[1] Mucinous carcinoma (MC) differs from AC in both clinical and pathological presentation. [2, 3] MC is more frequently found in the proximal colon and at a higher stage at presentation than AC. [2, 3] the response to therapies varies between MC and AC as patients with MC show a poorer response to palliative chemotherapy compared with AC, resulting in a worse survival. [4,5,6,7] These findings suggest a distinct genetic background of MC
We used high resolution array comparative genomic hybridization data that were generated from DNA isolated from formalin-fixed and paraffin-embedded (FFPE) primary tumors, which was hybridized against paired germ-line DNA samples
Summary
Colorectal cancer (CRC) is categorized by histological subtype according to the WHO classification. There are two major pathways through which genomic instability can occur in CRC, namely chromosomal instability (CIN) and microsatellite instability (MSI). CIN is found in the majority (~85%) of CRCs and is a type of genetic instability in which chromosomal aberrations accumulate, leading to an altered expression of tumor suppressor genes and oncogenes. Specific DNA CNAs that cause gene dosage effects in oncogenes and tumor suppressor genes, typically occur during adenoma to carcinoma progression, and are an integral part of the pathogenesis of CRC. Mucinous carcinoma (MC) is found in 10%–15% of colorectal cancer (CRC) patients. It differs from the common adenocarcinoma (AC) in histopathological appearance and clinical behavior
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