Predictors of germline status for hereditary melanoma: 5 years of multi-gene panel testing within the Italian Melanoma Intergroup

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W. Bruno¹  B. Dalmasso¹  M. Barile¹  V. Andreotti¹  L. Elefanti³  M. Colombino⁴  I. Vanni¹  E. Allavena²  F. Barbero¹  E. Passoni⁵  B. Merelli⁶  S. Pellegrini³  F. Morgese⁶  R. Danesi⁸  V. Calò⁹  V. Bazan^1,10  A.V. D’Elia^1,11  C. Molica^1,12  F. Gensini^1,13  E. Sala^1,14  V. Uliana^1,15  P.F. Soma^1,16  M. Genuardi^1,17  A. Ballestrero¹  F. Spagnolo¹  E. Tanda¹  P. Queirolo^1,19  M. Mandalà^1,12  I. Stanganelli^2,21  G. Palmieri⁴  C. Menin³  L. Pastorino¹  P. Ghiorzo¹ 

[1] IRCCS Ospedale Policlinico San Martino;University of Genoa, Department of Internal Medicine and Medical Specialties;Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV—IRCCS;Unit of Cancer Genetics, Institute of Genetics and Biomedical Research of the National Research Council;Dermatology Unit, Fondazione IRCCS Ca" Granda Ospedale Maggiore Policlinico;Oncology Unit;Department of Surgery, Oncology and Gastroenterology ,(DISCOG), University of Padua;Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori;Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo;Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo;Institute of Medical Genetics, ASUFC University Hospital of Udine;Medical Oncology Unit, S. Maria della Misericordia Hospital;Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence;Cytogenetics and Medical Genetics Unit;Medical Genetics Unit;Casa di Cura Gibiino;Fondazione Policlinico Universitario A. Gemelli IRCCS;Università Cattolica del Sacro Cuore, Department of Life Sciences and Public Health;Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS;Department of Surgery and Medicine, University of Perugia;Skin Cancer Unit, IRCCS IRST Istituto Scientifico Romagnolo per lo Studio dei Tumori ‘Dino Amadori’;Dermatologic Unit, Department of Medicine and Surgery, University of Parma

关键词: melanoma;    germline;    predictors;    gene panel;    CDKN2A;    susceptibility;   

DOI  :  10.1016/j.esmoop.2022.100525

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date.Materials and methods From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors.Results The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together.Conclusions Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.

【 授权许可】

CC BY|CC BY-NC-ND