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Molecular Characterization of Colorectal Signet-Ring Cell Carcinoma Using Whole-Exome and RNA Sequencing.

Transl Oncol. 2018 Aug;11(4):836-844. Epub 2018 May 07
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摘要


BACKGROUND:Signet-ring cell carcinoma (SRCC) is a very rare subtype of colorectal adenocarcinoma (COAD) with a poor clinical prognosis. Although understanding key mechanisms of tumor progression in SRCCs is critical for precise treatment, a comprehensive view of genomic alterations is lacking. MATERIALS AND METHODS:We performed whole-exome sequencing of tumors and matched normal blood as well as RNA sequencing of tumors and matched normal colonic tissues from five patients with SRCC. RESULTS:We identified major somatic alterations and characterized transcriptional changes at the gene and pathway level. Based on high-throughput sequencing, the pattern of mutations and copy number variations was overall similar to that of COAD. Transcriptome analysis revealed that major transcription factors, such as SRF, HNF4A, ZEB1, and RUNX1, with potential regulatory roles in key pathways, including focal adhesion, the PI3K-Akt signaling pathway, and the MAPK signaling pathway, may play a role in the tumorigenesis of SRCC. Furthermore, significantly upregulated genes in SRCCs were enriched for epithelial-mesenchymal transition genes, and accumulation of mucin in intracytoplasm was associated with the overexpression of MUC2. CONCLUSION:The results indicate that the molecular basis of colorectal SRCC exhibits key differences from that of consensus COAD. Our findings clarify important genetic features of particular abnormalities in SRCCs.

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