Genetic Predisposition to Numerous Large Ulcerating Basal Cell Carcinomas and Response to Immune Therapy
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.
immune therapy、malignant transformation gene-susceptibility、non-syndromic basal cell carcinoma、PTCH1、skin neoplasms
04
2023-05-30（万方平台首次上网日期，不代表论文的发表时间）
共6页
70-75
