Bridging genomics and phenomics of gastric carcinoma

International Journal of Cancer. Journal International Du Cancer
Junhun ChoKyoung-Mee Kim

Abstract

Genetic alterations are the starting point leading to numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their inter-relationships in gastric cancers (GC) are unclear. We performed massive parallel sequencing of 381 cancer-related genes and compared the results with clinical and pathologic findings in 330 GC. High tumor mutation burden (TMB) accounted for 11% of GC (n = 37) and all 19 MSI-H GCs were high TMB. High TMB was significantly more frequent in intestinal-type by Lauren, tumor with higher host cellular immune response, earlier AJCC stage and favorable prognosis. The most significantly mutated genes were TP53 (54%), ARID1A (23%), CDH1 (22%), PIK3CA (12%), RNF43 (10%) and KRAS (9%). For receptor tyrosine kinases, amplifications detected by immunohistochemistry were higher than sequencing (HER2, 9.1% vs. 5.8%; EGFR, 11.2% vs. 6.1%; FGFR2, 4.6% vs. 3.9%, c-MET, 3.4% vs. 0.9%). PTEN protein loss (22%) correlated well with underlying PTEN alterations while ATM loss (27%) was not significantly correlated with genetic alterations of ATM. p53 protein expression predicted alterations of TP53 with high sensitivity (97.8%) and low (15.9%) specificity. The poorly cohesive histology/CDH1...Continue Reading

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Citations

Nov 28, 2019·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Seon-Kyu KimYong Sung Kim
Nov 7, 2020·Journal of Pathology and Translational Medicine·Binnari KimKyoung-Mee Kim
Nov 15, 2020·Cellular and Molecular Gastroenterology and Hepatology·Victoria NeumeyerRaquel Mejías-Luque
Apr 8, 2021·Cellular and Molecular Life Sciences : CMLS·Olga Sokolova, Michael Naumann
May 19, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Soomin Ahn, Kyoung-Mee Kim
Jun 3, 2021·Journal of Clinical Medicine·Csongor György LengyelFahmi Seid
Sep 17, 2020·Clinical Breast Cancer·Adrienne N CobbPaul C Kuo
Nov 13, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·H KimK -M Kim

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