Journal of the American Academy of Dermatology
Volume 61, Issue 5 , Pages 775-782 , November 2009

Clinical genetic testing for familial melanoma in Italy: A cooperative study

  • William Bruno, MD, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • These authors contributed equally to this study.
    • Corresponding Author InformationCorrespondence to: William Bruno, MD, PhD.
    • ,
  • Paola Ghiorzo, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • These authors contributed equally to this study.
    • ,
  • Linda Battistuzzi, MS

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • These authors contributed equally to this study.
    • ,
  • Paolo A. Ascierto, MD

      Affiliations

    • Medical Oncology and Innovative Therapy Unit, National Tumor Institute “Fondazione Pascale,” Naples, Italy
    • ,
  • Monica Barile, MD

      Affiliations

    • Division of Cancer Prevention and Genetics, Chemoprevention, European Institute of Oncology, Milan, Italy
    • ,
  • Sara Gargiulo, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • Francesca Gensini, MD

      Affiliations

    • Section of Medical Genetics, Department of Pathophysiology, University of Florence, Florence, Italy
    • ,
  • Sara Gliori, MD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • Michele Guida, MD

      Affiliations

    • Medical Oncology Department, National Cancer Institute, Bari, Italy
    • ,
  • Maurizio Lombardo, MD

      Affiliations

    • Dermatology, “Ospedale di Circolo,” Varese, Italy
    • ,
  • Siranoush Manoukian, MD

      Affiliations

    • Medical Genetics Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy
    • ,
  • Chiara Menin, PhD

      Affiliations

    • Molecular Immunology and Diagnostic Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy
    • ,
  • Sabina Nasti, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • Paola Origone, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • Barbara Pasini, MD

      Affiliations

    • Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy
    • ,
  • Lorenza Pastorino, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • Bernard Peissel, MD

      Affiliations

    • Medical Genetics Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy
    • ,
  • Maria Antonietta Pizzichetta, MD

      Affiliations

    • Division of Medical Oncology, C-Preventive Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
    • ,
  • Paola Queirolo, MD

      Affiliations

    • Department of Medical Oncology A, National Institute for Cancer Research, Genoa, Italy
    • ,
  • Monica Rodolfo, PhD

      Affiliations

    • Medical Genetics Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy
    • ,
  • Antonella Romanini, MD

      Affiliations

    • Department of Oncology, Division of Medical Oncology, S. Chiara Hospital, Pisa, Italy
    • ,
  • Maria Chiara Scaini, PhD

      Affiliations

    • Section of Oncology, Department of Oncology and Surgical Sciences, University of Padua, Padua, Italy
    • ,
  • Alessandro Testori, MD

      Affiliations

    • Melanoma and Muscle-Cutaneous Sarcomas Division, European Institute of Oncology, Milan, Italy
    • ,
  • Maria Grazia Tibiletti, MD

      Affiliations

    • Anatomic Pathology Unit, University of Insubria, “Ospedale di Circolo,” Varese, Italy
    • ,
  • Daniela Turchetti, MD

      Affiliations

    • Medical Genetics, Bologna University, “Policlinico S. Orsola Malpighi”, Bologna, Italy
    • ,
  • Sancy A. Leachman, MD

      Affiliations

    • Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
    • ,
  • Giovanna Bianchi Scarrà, PhD

      Affiliations

    • Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
    • ,
  • IMI, the Italian Melanoma Intergroup

,Accepted 20 March 2009.

References 

  1. de Snoo FA, Hayward NK. Cutaneous melanoma susceptibility and progression genes. Cancer Lett. 2005;230:153–186
  2. Gruis NA, van der Velden PA, Sandkuijl LA, Prins DE, Weaver-Feldhaus J, Kamb A, et al. Homozygotes for CDKN2A (p16) germline mutation in Dutch familial melanoma kindreds. Nat Genet. 1995;10:351–353
  3. Borg A, Johannsson U, Johannson O, Häkansson S, Westerdahl J, Mäsbäck A, et al. Novel germline p16 mutation in familial malignant melanoma in southern Sweden. Cancer Res. 1996;56:2497–2500
  4. Ciotti P, Struewing JP, Mantelli M, Chompret A, Avril MF, Santi PL, et al. A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families. Am J Hum Genet. 2000;67:311–319
  5. Goldstein AM, Liu L, Shennan MG, Hogg D, Tucker MA, Struewing JP. A common founder for the V126D CDKN2A mutation in seven North American melanoma prone families. Br J Cancer. 2001;85:527–530
  6. Hashemi J, Bendahl PO, Sandberg T, Platz A, Linder S, Stierner U, et al. Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families. Genes Chromosomes Cancer. 2001;31:107–116
  7. Yakobson E, Eisenberg S, Isacson R, Halle D, Levy-Lahad E, Catane R, et al. A single Mediterranean, possibly Jewish, origin for the Val59Gly CDKN2A mutation in four melanoma-prone families. Eur J Hum Genet. 2003;11:288–296
  8. Ghiorzo P, Gargiulo S, Pastorino L, Nasti S, Cusano R, Bruno W, et al. E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma. Hum Mol Genet. 2006;15:2682–2689
  9. Gensini F, Sestini R, Piazzini M, Vignoli M, Chiarugi A, Brandani P, et al. The p.G23S CDKN2A founder mutation in high-risk melanoma families from Central Italy. Melanoma Res. 2007;17:387–392
  10. Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66:9818–9828
  11. Fargnoli MC, Chimenti S, Keller G, Soyer HP, Dal Pozzo V, Höfler H, et al. CDKN2a/p16INK4a mutations and lack of p19ARF involvement in familial melanoma kindreds. J Invest Dermatol. 1998;111:1202–1206
  12. Ghiorzo P, Ciotti P, Mantelli M, Heouaine A, Queirolo P, Rainero ML, et al. Characterization of Ligurian melanoma families and risk of occurrence of other neoplasia. Int J Cancer. 1999;83:441–448
  13. Della Torre G, Pasini B, Frigerio S, Donghi R, Rovini D, Delia D, et al. CDKN2A and CDK4 mutation analysis in Italian melanoma-prone families: functional characterization of a novel CDKN2A germ line mutation. Br J Cancer. 2001;85:836–844
  14. Mantelli M, Pastorino L, Ghiorzo P, Barile M, Bruno W, Gargiulo S, et al. Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian melanoma patients. Melanoma Res. 2004;14:443–448
  15. Majore S, De Simone P, Crisi A, Eibenschutz L, Binni F, Antigoni I, et al. CDKN2A/ CDK4 molecular study on 155 Italian subjects with familial and/or primary multiple melanoma. Pigment Cell Melanoma Res. 2008;21:209–211
  16. Bianchi-Scarrà G, Genuardi M, Pasini B, Tibiletti MG, Varesco L. Condizioni minime per la consulenza genetica in oncologia: Gruppo SIGU-ONC; 2000. Available from: URL:http://www.sigu.net. Accessed October 8, 2008.
  17. Bianchi-Scarrà G, Grammatico P, Genuardi M, Pasini B. Raccomandazioni per consulenza e test genetico nel melanoma ereditario: Gruppo SIGU-ONC; 2004. Available from: URL:http://www.sigu.net. Accessed October 8, 2008.
  18. Harland M, Mistry S, Bishop DT, Newton Bishop JA. A deep intronic mutation in CDKN2A is associated with disease in a subset of melanoma pedigrees. Hum Mol Genet. 2001;10:2679–2686
  19. Vignoli M, Scaini MC, Ghiorzo P, Sestini R, Bruno W, Menin C, et al. Genomic rearrangements of the CDKN2A locus are infrequent in Italian malignant melanoma families without evidence of CDKN2A/CDK4 point mutations. Melanoma Res. 2008;18:431–437
  20. Pastorino L, Bonelli L, Ghiorzo P, Queirolo P, Battistuzzi L, Balleari E, et al. CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. Pigment Cell Melanoma Res. 2008;21:700–709
  21. Huber J, Ramos ES. The P48T germline mutation and polymorphism in the CDKN2A gene of patients with melanoma. Braz J Med Biol Res. 2006;39:237–241
  22. Széll M, Balogh K, Dobozy A, Kemény L, Oláh J. First detection of the melanoma-predisposing proline-48-threonine mutation of p16 in Hungarians: was there a common founder either in Italy or in Hungary?. Melanoma Res. 2007;17:251–254
  23. Kefford RF, Newton Bishop JA, Bergman W, Tucker MA. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: a consensus statement of the melanoma genetics consortium. J Clin Oncol. 1999;17:3245–3251
  24. Kefford R, Bishop JN, Tucker M, Bressac-de Paillerets B, Bianchi-Scarrá G, Bergman W, et al. Genetic testing for melanoma. Lancet Oncol. 2002;3:653–654
  25. Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility; adopted on February 20, 1996. J Clin Oncol. 1996;14:1730–1736
  26. Olopade OI, Offit K, Garber JE. Genetic testing for susceptibility to cancer: task force on cancer genetics education. JAMA. 1998;279:1612–1613
  27. Gerstenblith MR, Goldstein AM, Tucker MA, Fraser MC. Genetic testing for melanoma predisposition: current challenges. Cancer Nurs. 2007;30:452–459
  28. Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996;12:97–99
  29. Soufir N, Avril MF, Chompret A, Demenais F, Bombled J, Spatz A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France: the French familial melanoma study group. Hum Mol Genet. 1998;7:209–216
  30. Molven A, Grimstvedt MB, Steine SJ, Harland M, Avril MF, Hayward NK, et al. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer. 2005;44:10–18
  31. Pjanova D, Engele L, Randerson-Moor JA, Harland M, Bishop DT, Newton Bishop JA, et al. CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population. Melanoma Res. 2007;17:185–191
  32. Leachman SA, Carucci J, Kohlmann W, Banks K, Asgari M, Bergman W, et al. Evidence-based selection of familial melanoma patients for genetic assessment. J Am Acad Dermatol. In press.
  33. Lesueur F, de Lichy M, Barrois M, Durand G, Bombled J, Avril MF, et al. The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. Br J Cancer. 2008;99:364–370
  34. Mistry SH, Taylor C, Randerson-Moor JA, Harland M, Turner F, Barrett JH, et al. Prevalence of 9p21 deletions in UK melanoma families. Genes Chromosomes Cancer. 2005;44:292–300
  35. Crocetti E, Capocaccia R, Casella C, De Lisi V, Ferretti S, Foca F, et al. Associazione Italiana Registri Tumori: I Tumori in Italia Rapporto 2006. Incidenza, mortalità e stime. Epidemiol Prev. 2006;30:1–147
  36. Holland EA, Schmid H, Kefford RF, Mann GJ. CDKN2A (P16(INK4a)) and CDK4 mutation analysis in 131 Australian melanoma probands: effect of family history and multiple primary melanomas. Genes Chromosomes Cancer. 1999;25:339–348
  37. Monzon J, Liu L, Brill H, Goldstein AM, Tucker MA, From L, et al. CDKN2A mutations in multiple primary melanomas. N Engl J Med. 1998;338:879–887
  38. Mantelli M, Barile M, Ciotti P, Ghiorzo P, Lantieri F, Pastorino L, et al. High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families. Am J Med Genet. 2002;107:214–221
  39. Puig S, Malvehy J, Badenas C, Ruiz A, Jimenez D, Cuellar F, et al. Role of the CDKN2A locus in patients with multiple primary melanomas. J Clin Oncol. 2005;23:3043–3051
  40. Ghiorzo P, Pastorino L, Bonelli L, Cusano R, Nicora A, Zupo S, et al. INK4/ARF germline alterations in pancreatic cancer patients. Ann Oncol. 2004;15:70–78

 Supported by the International Melanoma Genetics Consortium 01872 Network of Excellence Grant to Dr Bianchi Scarra'; Dr Scaini is supported by a Fondazione Italiana per la Ricerca sul Cancro (FIRC) fellowship.

 Conflicts of interest: None declared.

 Reprints not available from the authors.

PII: S0190-9622(09)00376-4

doi: 10.1016/j.jaad.2009.03.039

Journal of the American Academy of Dermatology
Volume 61, Issue 5 , Pages 775-782 , November 2009

Article Tools

* Image Usage & Resolution