title: Multiple primary tumors in a family with Li-Fraumeni syndrome with a TP53 germline mutation identified by next-generation sequencing.
abstract: Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies. We describe the clinical history of a patient who had 5 primary malignant cancers and a familiar history consistent with LFS. We analyzed the genomic DNA of the proband and her relatives by next-generation sequencing (NGS) technology using an enrichment protocol for the simultaneous sequencing of 94 genes involved in hereditary cancers. Genetic analysis of the proband revealed a TP53 germline mutation in exon 5 determining a nucleotide alteration at codon 175 (R175H), a hot spot mutation site related to LFS and a reported pathogenic mutation. The proband daughter's and brother's DNA did not carry the TP53 mutation but they had some rare variants in common with the proband, in addition to other variants with a still unclear role. In conclusion, we identified a TP53 mutation in a patient with multiple primary tumors and a family history characterized by a severe susceptibility to cancer. The genetic analysis by targeted NGS led to the identification of the genetic background and to the exclusion of a cancer risk for the family members. Targeted NGS represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype.
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Valentina
authors: V
authors: Zampiga
authors: Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Rita
authors: R
authors: Danesi
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Gianluca
authors: G
authors: Tedaldi
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Michela
authors: M
authors: Tebaldi
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Ilaria
authors: I
authors: Cangini
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Francesca
authors: F
authors: Pirini
authors: Palliative Care Unit, Savignano sul Rubicone Hospice, Savignano sul Rubicone (Forlì-Cesena) - Italy.
authors: Cristina
authors: C
authors: Pittureri
authors: Palliative Care Unit, Savignano sul Rubicone Hospice, Savignano sul Rubicone (Forlì-Cesena) - Italy.
authors: Elena
authors: E
authors: Amaducci
authors: General Practitioner, AUSL Romagna, Longiano (Forlì-Cesena) - Italy.
authors: Luciano
authors: L
authors: Guidi
authors: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Marina
authors: M
authors: Faedi
authors: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Dino
authors: D
authors: Amadori
authors: Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Fabio
authors: F
authors: Falcini
authors: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena) - Italy.
authors: Daniele
authors: D
authors: Calistri
mesh_terms: D000328:Adult; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53