Microsatellite frameshift variants in SGO1 of gastric cancer are not always associated with MSI status

Aims Although frameshift variants in the microsatellite area of shugoshin 1 (SGO1) have been reported in the context of microsatellite instability-high (MSI-H)/deficient mismatch repair gastrointestinal cancer, most have been evaluated only in early stage I–III patients, and only two of its five microsatellite regions have been evaluated. Therefore, we investigated the frequency and MSI status of microsatellite frameshift variants in gastric cancer cases, including stage IV. Methods In a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software. Results A frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delA SGO1 variant. However, c.973delA SGO1 variant was also observed in four cases of microsatellite stable. Conclusion Our study shows that SGO1 frameshift variants are not always associated with MSI status.

[1]  A. Bass,et al.  Genomics and Targeted Therapies in Gastroesophageal Adenocarcinoma. , 2019, Cancer discovery.

[2]  D M Parkin,et al.  Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods , 2018, International journal of cancer.

[3]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[4]  A. Barzi,et al.  Outlooks on Epstein-Barr virus associated gastric cancer. , 2018, Cancer treatment reviews.

[5]  Gad Getz,et al.  Analysis of somatic microsatellite indels identifies driver events in human tumors , 2017, Nature Biotechnology.

[6]  Kazuhiro Yoshida,et al.  Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. , 2017, The lancet. Gastroenterology & hepatology.

[7]  Sheng-fang Jiang,et al.  Impact of Age on Clinicopathological Features and Survival of Patients with Noncardia Gastric Adenocarcinoma , 2014, Journal of gastric cancer.

[8]  Naotoshi Sugimoto,et al.  Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. , 2014, The Lancet. Oncology.

[9]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of gastric adenocarcinoma , 2014, Nature.

[10]  K. Muro,et al.  Phase II trial of nanoparticle albumin-bound paclitaxel as second-line chemotherapy for unresectable or recurrent gastric cancer , 2014, Cancer science.

[11]  Takashi Takahashi,et al.  SGOL1 variant B induces abnormal mitosis and resistance to taxane in non-small cell lung cancers , 2013, Scientific Reports.

[12]  N. Yoo,et al.  Frameshift mutations of chromosome cohesion-related genes SGOL1 and PDS5B in gastric and colorectal cancers with high microsatellite instability. , 2013, Human pathology.

[13]  喜彦 前原,et al.  【消化器癌とサイトメトリー】 消化器癌におけるDNA aneuploidyの意義 , 2012 .

[14]  C. Rao,et al.  Haploinsufficiency of SGO1 results in deregulated centrosome dynamics, enhanced chromosomal instability and colon tumorigenesis , 2012, Cell cycle.

[15]  H. Sugimura,et al.  A novel tumor-derived SGOL1 variant causes abnormal mitosis and unstable chromatid cohesion , 2011, Oncogene.

[16]  Silvia Polakova,et al.  Merotelic kinetochore attachment: causes and effects , 2011, Trends in cell biology.

[17]  Yoshinori Watanabe,et al.  Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation , 2010, Nature.

[18]  S. Noh,et al.  Analysis of demographic characteristics in 3242 young age gastric cancer patients in Korea. , 2010, World journal of gastroenterology.

[19]  Yoshinori Watanabe,et al.  Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin , 2010, Science.

[20]  W. Earnshaw,et al.  Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins , 2009, Current opinion in cell biology.

[21]  D. Cleveland,et al.  Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis , 2009, Nature Reviews Molecular Cell Biology.

[22]  David Pellman,et al.  A Mechanism Linking Extra Centrosomes to Chromosomal Instability , 2009, Nature.

[23]  F. Merchant,et al.  Overexpression and Mislocalization of the Chromosomal Segregation Protein Separase in Multiple Human Cancers , 2009, Clinical Cancer Research.

[24]  M. Shimura,et al.  Heterochromatin links to centromeric protection by recruiting shugoshin , 2008, Nature.

[25]  F. Kittrell,et al.  Overexpression of Separase induces aneuploidy and mammary tumorigenesis , 2008, Proceedings of the National Academy of Sciences.

[26]  H. Sugimura,et al.  Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer , 2008, Gut.

[27]  G. Parmigiani,et al.  Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers , 2008, Proceedings of the National Academy of Sciences.

[28]  J. Brenton,et al.  Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. , 2007, Cancer cell.

[29]  Tohru Natsume,et al.  Shugoshin collaborates with protein phosphatase 2A to protect cohesin , 2006, Nature.

[30]  Karl Mechtler,et al.  Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I , 2006, Nature.

[31]  Lior Pachter,et al.  Reference based annotation with GeneMapper , 2006, Genome Biology.

[32]  C. Swanton,et al.  Chromosomal Instability, Colorectal Cancer and Taxane Resistance , 2006, Cell cycle.

[33]  Kim Nasmyth,et al.  Shugoshin Prevents Dissociation of Cohesin from Centromeres During Mitosis in Vertebrate Cells , 2005, PLoS biology.

[34]  T. Kitajima,et al.  Human Bub1 Defines the Persistent Cohesion Site along the Mitotic Chromosome by Affecting Shugoshin Localization , 2005, Current Biology.

[35]  N. Rahman,et al.  Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B , 2004, Nature Genetics.

[36]  J. Yokota,et al.  A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus. , 2004, Carcinogenesis.

[37]  T. Mitchison,et al.  Vertebrate Shugoshin Links Sister Centromere Cohesion and Kinetochore Microtubule Stability in Mitosis , 2004, Cell.

[38]  H. Saya,et al.  Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint , 2004, Cancer Research.

[39]  T. Kitajima,et al.  The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis , 2004, Nature.

[40]  H. Grabsch,et al.  Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer—association with tumour cell proliferation , 2003, The Journal of pathology.

[41]  S. Tsao,et al.  Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells. , 2002, Cancer research.

[42]  H. Ellegren.  Microsatellite mutations in the germline: implications for evolutionary inference. , 2000, Trends in genetics : TIG.

[43]  S Srivastava,et al.  A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. , 1998, Cancer research.

[44]  N. Lawrence,et al.  Tubulin as a target for anticancer drugs: Agents which interact with the mitotic spindle , 1998, Medicinal research reviews.

[45]  K. Kinzler,et al.  Genetic instability in colorectal cancers , 1997, Nature.

[46]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.

[47]  H. Sugimura,et al.  Suppression of hydroxyurea-induced centrosome amplification by NORE1A and down-regulation of NORE1A mRNA expression in non-small cell lung carcinoma. , 2011, Lung cancer.

[48]  F. Bosman,et al.  WHO Classification of Tumours of the Digestive System , 2010 .

[49]  T. Fojo,et al.  Raf-1/bcl-2 phosphorylation: a step from microtubule damage to cell death. , 1997, Cancer research.