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Mutational and expressional analysis of SMC 2 gene in gastric and colorectal cancers with microsatellite instability
Author(s) -
Je Eun Mi,
Yoo Nam Jin,
Lee Sug Hyung
Publication year - 2014
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12193
Subject(s) - frameshift mutation , microsatellite instability , biology , dna mismatch repair , genetics , gene , microbiology and biotechnology , mutation , cancer research , dna repair , microsatellite , allele
Structural maintenance of chromosomes 2 ( SMC 2 ) gene encodes condensin complexes that are required for proper chromosome segregation and maintenance of chromosomal stability. Although cells with defective chromosome segregation become aneuploid and are prone to harbor chromosome instability, pathologic implications of SMC 2 gene alterations are largely unknown. In a public database, we found that SMC 2 gene had mononucleotide repeats that could be mutated in cancers with microsatellite instability ( MSI ). In this study, we analyzed these repeats in 32 gastric cancers ( GC ) with high MSI ( MSI ‐H), 59 GC with low MSI ( MSI ‐L)/stable MSI ( MSS ), 43 colorectal cancers ( CRC ) with MSI ‐H and 60 CRC with MSI ‐L/ MSS by single‐strand conformation polymorphism ( SSCP ) and DNA sequencing. We also analyzed SMC 2 protein expression in GC and CRC tissues using immunohistochemistry. We found SMC 2 frameshift mutations in two GC and two CRC that would result in truncation of SMC 2. The mutations were detected exclusively in MSI ‐H cancers, but not in MSI ‐L/ MSS cancers. Loss of SMC 2 expression was observed in 22% of GC and 25% of CRC . Of note, all of the cancers with SMC 2 frameshift mutations displayed loss of SMC 2 expression. Also, both GC and CRC with MSI ‐H had significantly higher incidences in SMC 2 frameshift mutations and loss of SMC 2 expression than those with MSI ‐L/ MSS . Our data indicate that SMC 2 gene is altered by both frameshift mutation and loss of expression in GC and CRC with MSI ‐H, and suggest that SMC 2 gene alterations might be involved in pathogenesis of these cancers.