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

• 作者: Bahar Dasgeb Youssefian Leila Amir Hossein Saeidian Jun Kang Wenyin Shi Elizabeth Shoenberg Adam Ertel Paolo Fortina Hassan Vahidnezhad Jouni Uitto
• 来源期刊: 国际皮肤性病学杂志（英文）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Original Articles
• 页码范围: 70-75
• 页数: 6页
• 语种: 中文
• DOI: 10.1097/JD9.0000000000000170

摘要

Objective:Well-defined germ-line mutations in the PTCH1 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 homozygous PTCH1 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,and GALNT12)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,and GALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple,unusually large BCCs.