Alternative transcript imbalance underlying breast cancer susceptibility in a family carrying PALB2 c.3201+5G&gt;T

Duran-Lozano, Laura; Montalban, Gemma; Bonache, Sandra; Moles‐Fernández, Alejandro; Tenés, Anna; Castroviejo-Bermejo, Marta; Carrasco, Estela; López‐Fernández, Adrià; Torres-Esquius, Sara; Gadea, Neus; Stjepanovic, Neda; Balmañà, Judith; Gutiérrez‐Enríquez, Sara; Dı́ez, Orland

doi:10.1007/s10549-018-05094-8

Cited by 6 publications

(1 citation statement)

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“…This guideline describes the classification of variants based on evidences, such as population, in silico, functional and segregation analysis. Among all the criteria, it is worth noting that co-segregation and loss of heterozygosity analysis have been widely used and have an important role in the classification of variants of tumor suppressor genes identified in high risk families (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Using Co-segregation and Loss of Heterozygosity Analysis to Define the Pathogenicity of Unclassified Variants in Hereditary Breast Cancer Patients

et al. 2020

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The use of gene panels introduces a new dilemma in the genetics field due to the high frequency of variants of uncertain significance (VUS). The objective of this study was to provide evidence that may help in the classification of these germline variants in terms of their clinical impact and association with the disease in question. A total of 52 unrelated women at-risk for HBOC and negative for BRCA1/BRCA2 pathogenic variants were evaluated through a gene panel comprising 14 breast and/or ovarian cancer susceptibility genes. Of the 453 germline variants identified, 15 variants (classes 3, 4, and 5) in the ATM, BRIP1, CHEK2, MRE11A, MUTHY, PALB2, RAD50 , and RAD51C genes were evaluated via databases, co-segregation studies and loss of heterozygosity in the tumor. The co-segregation analysis allowed the establishment of an association with the presence of variants and the risk of cancer for variant c.316C>T in the BRIP1 gene. Four variants of uncertain significance showed loss of heterozygosity in the tumor ( ATM c.4709T>C; CHEK2 c.1036C>T; PALB2 c.1001A>G, and RAD50 c.281T>C), which is an indication of pathogenicity. Thus, the present study provides novel evidence that favors the association of variants in moderate-risk genes with the development of hereditary breast cancer.

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Section: Introductionmentioning

confidence: 99%