Genetic Predisposition to Numerous Large Ulcerating Basal Cell Carcinomas and Response to Immune Therapy  

作　　者：Bahar Dasgeb Leila Youssefian Amir Hossein Saeidian Jun Kang Wenyin Shi Elizabeth Shoenberg Adam Ertel Paolo Fortina Hassan Vahidnezhad Jouni Uitto 

机构地区：[1]Department of Surgical Oncology,Rutgers Cancer Institute of New Jersey,New Brunswick,NJ 08903,USA [2]Department of Dermatology and Cutaneous Biology,Sidney Kimmel Medical College,and Jefferson Institute of Molecular Medicine,Thomas Jefferson University,Philadelphia,PA 19107,USA [3]Genetics,Genomics and Cancer Biology PhD Program,Thomas Jefferson University,Philadelphia,PA 19107,USA [4]Department of Radiation Oncology,Thomas Jefferson University,Philadelphia,PA,USA [5]Department of Internal Medicine,Mercy Medical Center,Baltimore,MD 21202,USA [6]Department of Cancer Biology,Sidney Kimmel Cancer Center,Thomas Jefferson University,Philadelphia,PA 19107,USA

出　　处：《International Journal of Dermatology and Venereology》2021年第2期70-75,共6页国际皮肤性病学杂志（英文）

基　　金：The study was supported by NIH R01 IA143810;the Department of Dermatology and Cutaneous Biology,Thomas Jefferson University Institutional funds.

摘　　要：Objective:Well-defined germ-line mutations in thePTCH1 gene are associated with syndromic multiple basal cell carcinomas(BCCs).Here,we used whole exome sequencing(WES)to identify the role of patched-1 in patients with multiple,unusually large BCCs.Methods:A 72-year old patient presenting with numerous BCCs progressing to large ulcerating lesions was enrolled.WES was used to identify the pathogenic gene locus.Results:Genetic work-up by WES identified a homozygousPTCH1 nonsense mutation in the tumor tissue but not present in her blood cells or in non-lesional skin.In addition,heterozygous missense mutations were identified in three cancer-associated genes(EPHB2,RET,andGALNT12)in blood cells as well as in lesional and non-lesional skin.We also tested systemic immune therapy as a potentially beneficial approach to treat patients with numerous large BCCs on scatted areas of involvement.A rapid and sustained response to nivolumab was noted,suggesting that it is an efficacious drug for long-term therapeutic outcome.Conclusion:PTCH1,EPHB2,RET,andGALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple,unusually large BCCs.

关 键 词：immune therapy malignant transformation gene-susceptibility non-syndromic basal cell carcinoma PTCH1 skin neoplasms 

分 类 号：R739.5[医药卫生—肿瘤]