Distinct Non-Clock-Like Signatures of the Basal Cell Carcinomas from Three Sisters with a Lethal Gorlin-Goltz Syndrome

Published: 25 July 2022| Version 3 | DOI: 10.17632/5s4pk4rj32.3
Kexin Peng,


We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. Supplementary Information: Additional file 1. Somatic single nucleotide variant (SNV) sites in whole exome sequencing of matched BCC and ANCT. Additional file 2. Somatic loss of heterozygosity (LOH) in whole exome sequencing of matched BCC and ANCT.



Exome Sequencing