Comprehensive Genomic and Phenotypic Characterization of Germline FH Deletion in Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)

This study evaluated the prevalence and clinical phenotype of FH deletions in HLRCC patients. Patients with phenotypic manifestations consistent with HLRCC who lacked detectable germline FH intragenic mutations were investigated for FH deletion. A series of 28 patients from 13 families were evaluated using a combination of a comparative genomic hybridization (CGH) array and/or CLIA‐approved FH deletion/duplication analyses. Thirteen distinct germline deletions were identified in the 13 UOB families, including 11 complete FH gene deletions and two partial FH gene deletions. The size of eight evaluated complete FH deletions varied from ∼4.74Mb to 249kb, with all deletions resulting in additional gene losses. Two partial FH gene deletions were identified, with one resulting in loss of exon 1 and the upstream region of the FH gene only. Kidney cancer was diagnosed in 9 (32%) of 28 patients and 7 (54%) of 13 families possessing either complete or partial FH deletions. Cutaneous and uterine leiomyomas were observed at similar rates to those in FH point mutation families. Complete or partial FH gene alterations in HLRCC families are associated with all of the canonical HLRCC manifestations, including Type 2 papillary kidney cancer and should be screened for in any patient at‐risk for this disorder. This article is protected by copyright. All rights reserved.
Source: Genes, Chromosomes and Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research