Genomic and functional study of rare deleterious germline mutations in candidate genes associated with familial risk for esophageal carcinoma

Dr Ko, Josephine Mun Yee   (Principal Investigator (PI))

Professor Huen Michael Shing Yan   (Co-Investigator)

Emeritus Professor Lung Maria Li   (Co-Investigator)

36

2018-01-01

971720

Genomic and functional study of rare deleterious germline mutations in candidate genes associated with familial risk for esophageal carcinoma

Cancer Predisposition Gene, Deep sequencing, Esophageal Cancer (EC), Familial cancer, Genomic Instability

Cancer,Genomics

Biology and Medicine (M)

17118517

General Research Fund (GRF)

2017

Completed

1 To understand the genetic basis of familial ESCC predisposition and provide mechanistic insight for cancer causation by study of the mutation prevalence of three novel candidate CPGs for familial ESCC: RAD50, ZNF208, and CNTRL in large independent cohorts of familial ESCC and sporadic ESCC in Henan to assess their role as CPGs for ESCC risk; to identify potential biomarkers for early diagnosis and prevention. 2 To gain insight of the potential therapeutic impact of RAD50 mutants by investigating the dominant-negative effect for LOF RAD50 mutants for sensitization of ESCC cell lines to cisplatin and PARP inhibitors; to identify potential new treatment options by exploring synthetic lethality targeting ATM/CDK1 for checkpoint inhibition of ATR signaling for hypersensitivity of ESCC cells carrying defective MRN function to cell death upon DSB stimuli.