title: Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report.
abstract: The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM).Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility.Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility.Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer.
authors.affiliation: Lung Cancer Unit, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova Centre for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan Department of Internal Medicine and Medical Specialties (DIMI), Università di Genova IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova Department of Pathology, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova Laboratory of Tumor Epigenetics, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro and Department of Health Sciences, Università di Genova, Genova, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Vanni
authors.forename: Simona
authors.initials: S
authors.lastname: Coco
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonfiglio
authors.forename: Davide
authors.initials: D
authors.lastname: Cittaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Genova
authors.forename: Federica
authors.initials: F
authors.lastname: Biello
authors.forename: Marco
authors.initials: M
authors.lastname: Mora
authors.forename: Valeria
authors.initials: V
authors.lastname: Rossella
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Dal Bello
authors.forename: Anna
authors.initials: A
authors.lastname: Truini
authors.forename: Barbara
authors.initials: B
authors.lastname: Banelli
authors.forename: Dejan
authors.initials: D
authors.lastname: Lazarevic
authors.forename: Angela
authors.initials: A
authors.lastname: Alama
authors.forename: Erika
authors.initials: E
authors.lastname: Rijavec
authors.forename: Giulia
authors.initials: G
authors.lastname: Barletta
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D059472:Exome; D016162:Genes, Wilms Tumor; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects