Frameshift mutation of WISP3 gene and its regional heterogeneity in gastric and colorectal cancers

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• 作者：Ju Hwa Lee ; BS^a ; Youn Jin Choi ; MD^a ; Eun Mi Je ; MS^a ; Ho Shik Kim ; MD^b ; Nam Jin Yoo ; MD^a ; Sug Hyung Lee ; MD^a ; ^{suhulee@catholic.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：WISP3 ; Colon cancer ; Somatic mutation ; Gastric cancer ; Heterogeneity
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：50
• 期：Complete
• 页码：146-152
• 全文大小：1178 K

文摘

WISP3 is involved in many cancer-related processes including epithelial-mesenchymal transition, cell death, invasion, and metastasis and is considered a tumor suppressor. The aim of our study was to find whether WISP3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRCs). WISP3 gene possesses a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 156 CRCs, and found that GCs (8.8%) and CRCs (10.5%) with MSI-H, but not those with microsatellite stable/low MSI, harbored a frameshift mutation. We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the WISP3 mutation exhibited regional ITH in 25% of the CRCs. In immunohistochemistry, loss of WISP3 expression was identified in 24% of GCs and 21% of CRCs. The loss of expression was more common in those with WISP3 mutation than with wild-type WISP3 and those with MSI-H than with microsatellite stable/low MSI. Our data indicate that WISP3 harbored not only frameshift mutation but also mutational ITH and loss of expression, which together might play a role in tumorigenesis of GC and CRC with MSI-H by inhibiting tumor suppressor functions of WISP3. Our data also suggest that mutation analysis in multiregions is needed for a proper evaluation of mutation status in GC and CRC with MSI-H.