title: Identification of the first case of germline duplication of BRCA1 exon 13 in an Italian family.
abstract: In this work we report for the first time a family in Italy with the BRCA1 ins6kbEx13 mutation, a recurrent founder mutation originating from northern Britain. After the initial identification of exon 13 duplication by multiplex ligation-dependent probe amplification (MLPA assay), we confirmed the identity of the alteration with the previously published BRCA1 ins6kbEx13 mutation, by mutation specific PCR and RT-PCR assays and by haplotype analysis. As rarely reported previously, the MLPA assay was also used to examine DNA from formalin fixed paraffin embedded (FFPE) normal tissues of other affected subjects in the family and it was the only effective method to perform a complete segregation analysis of the BRCA1 ins6kbEx13 mutation in the family. A combination of different approaches including MLPA analysis, haplotype analysis and LOH study on tumor samples of all the affected members allowed to reassess the maternal transmission of the mutation expected by the pedigree analysis. Moreover, detailed morphological analysis of breast cancers of BRCA1 ins6kbEx13 mutation carriers demonstrated a rare histological variant of breast carcinomas that has never been described in patients carrying BRCA1 mutations. Our study confirms the MLPA technique as a reliable and effective method for a primary screening for BRCA1 rearrangements also by using FFPE tissues and strongly suggests that histo-pathological, immunonohistochemical and molecular information from FFPE tumor tissues should be more often considered and integrated into routine diagnostic practice of hereditary tumors.
authors.affiliation: Department of Human Morphology, Anatomic Pathology Unit, Centro Insubre di Biotecnologie per la Salute Umana, Ospedale di Circolo, University of Insubria, Via O. Rossi, 9, 21100, Varese, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cerutti
authors.forename: Nora
authors.initials: N
authors.lastname: Sahnane
authors.forename: Ileana
authors.initials: I
authors.lastname: Carnevali
authors.forename: Daniela
authors.initials: D
authors.lastname: Furlan
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Chiaravalli
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D020440:Gene Duplication; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction