Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired homologous recombination repair in fragile histidine triad-negative sebaceous gland carcinomas

The British Journal of Dermatology
K BeckerW G Ballhausen

Abstract

Sebaceous gland carcinomas represent rare malignancies of the skin and some 60% of them demonstrate high-grade microsatellite instability on the background of a defective mismatch repair system. However, a significant fraction of periocular sebaceous gland carcinomas exhibits microsatellite stability associated with a frequent loss of the candidate tumour suppressor fragile histidine triad (FHIT). We hypothesized that in those sebaceous gland carcinomas with microsatellite stability and loss of FHIT, effector molecules participating in homologous recombination repair (HRR), such as BRCA1/2, could be somatically inactivated. A pilot series of 10 paraffin-embedded sebaceous gland carcinoma specimens with a defined FHIT status was studied for loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We sequenced the coding exons 5-8 of the p53 gene. Sebaceous gland carcinomas with FHIT negativity displayed LOH and biallelic deletions of the BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG transition was identified in one of seven seb...Continue Reading

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Citations

Mar 24, 2012·The American Journal of Dermatopathology·Sara C ShalinAlexander J Lazar
Sep 7, 2011·Diagnostic Pathology·Dongjin SungFederico Gonzalez-Fernandez
Oct 6, 2015·International Journal of Cancer. Journal International Du Cancer·Leilei ZhangXianqun Fan
Jun 3, 2009·Cancer Science·Hiroshi OkumuraKay Huebner
Oct 2, 2014·The Journal of Pathology·Manuela TumiatiSergey G Kuznetsov
Jun 18, 2016·Pathology·Nathan Tobias HarveyBenjamin Andrew Wood
Sep 23, 2018·Genes, Chromosomes & Cancer·Joshua C Saldivar, Dongju Park

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