Early-Stage Induction of SWI/SNF Mutations during Esophageal Squamous Cell Carcinogenesis

PloS One
Hidetsugu NakazatoToshikazu Ushijima

Abstract

The SWI/SNF chromatin remodeling complex is frequently inactivated by somatic mutations of its various components in various types of cancers, and also by aberrant DNA methylation. However, its somatic mutations and aberrant methylation in esophageal squamous cell carcinomas (ESCCs) have not been fully analyzed. In this study, we aimed to clarify in ESCC, what components of the SWI/SNF complex have somatic mutations and aberrant methylation, and when somatic mutations of the SWI/SNF complex occur. Deep sequencing of components of the SWI/SNF complex using a bench-top next generation sequencer revealed that eight of 92 ESCCs (8.7%) had 11 somatic mutations of 7 genes, ARID1A, ARID2, ATRX, PBRM1, SMARCA4, SMARCAL1, and SMARCC1. The SMARCA4 mutations were located in the Forkhead (85Ser>Leu) and SNF2 family N-terminal (882Glu>Lys) domains. The PBRM1 mutations were located in a bromodomain (80Asn>Ser) and an HMG-box domain (1,377Glu>Lys). For most mutations, their mutant allele frequency was 31-77% (mean 61%) of the fraction of cancer cells in the same samples, indicating that most of the cancer cells in individual ESCC samples had the SWI/SNF mutations on one allele, when present. In addition, a BeadChip array analysis revealed tha...Continue Reading

References

Oct 15, 2010·The New England Journal of Medicine·Kimberly C WiegandDavid G Huntsman
Jun 10, 2011·Nature Reviews. Cancer·Boris G Wilson, Charles W M Roberts
Dec 30, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Toshikazu Ushijima, Naoko Hattori
Aug 28, 2012·Nature Genetics·Jian HuangZe-Guang Han
Oct 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaofeng WangCharles W M Roberts
Dec 7, 2013·PloS One·Takamasa TakahashiToshikazu Ushijima
Feb 11, 2014·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Yukie YodaToshikazu Ushijima
Mar 25, 2014·Nature Genetics·Petar JelinicDouglas A Levine
Apr 2, 2014·Nature Genetics·De-Chen LinH Phillip Koeffler
Jun 24, 2014·Nature Genetics·Jamie M J WeaverUNKNOWN OCCAMS consortium
Aug 26, 2014·Nature Genetics·Yi-Bo GaoJie He
Dec 3, 2014·Cancer Letters·Hideyuki TakeshimaToshikazu Ushijima

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Datasets Mentioned

BETA
KYSE220

Methods Mentioned

BETA
Assay
PCR
amplicon sequencing

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