Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer

2011 ◽  
Vol 43 (12) ◽  
pp. 1219-1223 ◽  
Author(s):  
Kai Wang ◽  
Junsuo Kan ◽  
Siu Tsan Yuen ◽  
Stephanie T Shi ◽  
Kent Man Chu ◽  
...  
2020 ◽  
Vol 26 (41) ◽  
pp. 6414-6430
Author(s):  
Jin Bian ◽  
Jun-Yu Long ◽  
Xu Yang ◽  
Xiao-Bo Yang ◽  
Yi-Yao Xu ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1689 ◽  
Author(s):  
Bianca Grosser ◽  
Meike Kohlruss ◽  
Julia Slotta-Huspenina ◽  
Moritz Jesinghaus ◽  
Nicole Pfarr ◽  
...  

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.


2020 ◽  
Vol 8 (22) ◽  
pp. 1484-1484
Author(s):  
Zhenxin Zhu ◽  
Hongbing Fu ◽  
Shengzhou Wang ◽  
Xinxin Yu ◽  
Qing You ◽  
...  

Oncotarget ◽  
2018 ◽  
Vol 9 (27) ◽  
pp. 19427-19442 ◽  
Author(s):  
Magdalena Cisło ◽  
Agata Anna Filip ◽  
George Johan Arnold Offerhaus ◽  
Bogumiła Ciseł ◽  
Karol Rawicz-Pruszyński ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4082-4082
Author(s):  
David Paul Kelsen ◽  
Kasmintan A. Schrader ◽  
Raya Khanin ◽  
Laura H. Tang ◽  
Erin E. Salo-Mullen ◽  
...  

4082 Background: CDH1 encodes E-cadherin; mutations (CDH1mut) increase the risk of diffuse gastric (DGC) and lobular breast cancers. Life-time risk of DGC is estimated at 80%. Current recommendations are prophylactic gastrectomy (PG) in CDH1mut carriers after age 20. Foci of DGC are found in some PG; others have none at PG, and some CDH1mut without PG never develop cancer. Identifying risk modifying alleles or other genomic events which increase the risk of DGC may improve understanding of DGC and may provide a biomarker for when to perform PG. Methods: For a Gastric Cancer Registry, we collected family pedigrees, germline DNA and FFPE tumor from CDH1mut DGC patients (pts) and their families. From 24 families, with 52 CDH1mut individuals, we identified 4 families in which a young CDH1mut pt developed advanced DGC while their CDH1mut parent and siblings had no clinical evidence of DGC. Several relatives had undergone PG with no DGC found. We hypothesize that there are risk modifying alleles and/or a “second hit” that causes variable penetrance and early onset of DGC in the young CDH1mut pts. Whole genome sequencing was performed on germ line DNA (Complete Genomics, Inc. Mountain View, CA); and whole exome sequencing on tumor specimens (MSKCC). Results: To date, 4 DGC pts and 8 relatives from 4 families have been studied. All 4 affected pts were women (ages 17, 25, 27, 42); their unaffected CDH1mut parents were 41, 51, 54, and 70 years old. The families are of Kenyan, Scandinavian, Italian, Eastern European, and Scottish origin. CDH1 mutations for the pts and their families were confirmed on WGS, and were as follows: 1451C>A(pro484his);c. 1792C>T (arg598ter);c. 1893dupA in exon 12;c. 1565+1G>A (IVS10+1G>A). Analysis of germline DNA for modifying alleles is being performed (Ingenuity Systems, Redwood, Ca.); whole exome sequencing of tumor to identify a possible "second hit" is underway. These data will be presented. Conclusions: Since at least some older pts with proven CDH-1mut do not develop DGC while their children do, CGH-1mut alone may not be sufficient to cause early onset DGC. We hope to identify the additional genomic events associated with early onset advanced DGC. Supported in part by grants from the Gerstner and DeGregorio Foundations.


2020 ◽  
Author(s):  
Yin Jin ◽  
Liping Tao ◽  
Shengnan Li ◽  
Shuqing Jin ◽  
Weiyang Cai

Abstract Background: The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor- infiltrating immune cells (TIICs) activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer (GC) immune cell infiltration has not been identified so far.Reuslts: In this study, we comprehensively analyzed the TIICs abundance in GC for the first time by CIBERSORT. The fraction of TIICs subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes. Unsupervised clustering analysis revealed there existed three distinct TIICs subgroups with distinct survival patterns. We also focused on analyzing the prognostic influence of TIICs in TP53, TTP and PIK3CA molecular subtypes.Conclusions: Collectively, our data explored the differences of TIICs in GC, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.


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