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Hereditary Skin Cancer

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Molecular Pathology in Clinical Practice

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Abstract

Skin cancer can be divided into three categories: basal cell carcinoma, squamous cell carcinoma, and melanoma. Because of the heterogeneity of the skin cancer phenotypes as well as the unknown exact correlation to genotypes, genetic testing is not offered on routine bases for all types of skin cancers. Several approaches are being used by clinicians, to determine the possible genetic components, which may be involved after complete skin examination by a dermatologist as a screening tool for skin cancer and family history determination. Molecular genetics of melanoma can be both diagnostically and therapeutically useful. When candidate’s genes are known, according to the skin cancer phenotypes or the syndrome, Sanger sequencing and gene copy number variations (MLPA or RT-PCR) are applied. More recently, the use of comparative genomic hybridization (CGH), analysis of copy number in known miRNA genes, and exome sequencing, followed by screening of targeted genes in melanoma, helps to elucidate the genetic background of several skin cancers and the appropriate therapeutic approach. Referral of individuals affected or at risk for skin cancers to a genetic counselor or hereditary cancer center that routinely tests skin cancers patients is recommended.

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References

  1. Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146(3):283–7.

    Article  PubMed  Google Scholar 

  2. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch Dermatol. 1995;131(2):164–9.

    Article  CAS  PubMed  Google Scholar 

  3. Lindelöf B, Sigurgeirsson B, Tegner E, et al. PUVA and cancer risk: the Swedish follow-up study. Br J Dermatol. 1999;141(1):108–12.

    Article  PubMed  Google Scholar 

  4. Grodstein F, Speizer FE, Hunter DJ. A prospective study of incident squamous cell carcinoma of the skin in the nurses’ health study. J Natl Cancer Inst. 1995;87(14):1061–6.

    Article  CAS  PubMed  Google Scholar 

  5. Habif, TP. Clinical dermatology. 5th edn. St. Louis: Mosby/Elsevier. 2009.

    Google Scholar 

  6. Stacey SN, Sulem P, Masson G, Gudjonsson SA, et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet. 2009;41:909–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Rafnar T, Sulem P, Stacey SN, Geller F, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009;41:221–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Friedman E, Gejman PV, Martin GA, McCormick F. Nonsense mutations in the C-terminal SH2 region of the GTPase activating protein (GAP) gene in human tumours. Nat Genet. 1993;5:242–7.

    Article  CAS  PubMed  Google Scholar 

  9. Ding L, Kim M, Kanchi KL, et al. Clonal architecures and driver mutations in metastatic melanomas.

    Google Scholar 

  10. Aszterbaum M, Rothman A, Johnson RL, Fisher M, et al. Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol. 1998;110:885–8.

    Article  CAS  PubMed  Google Scholar 

  11. Smyth I, Narang MA, Evans T, Heimann C, et al. Isolation and characterization of human Patched 2 (PTCH2), a putative tumour suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Genet. 1999;8:291–7.

    Article  CAS  PubMed  Google Scholar 

  12. Kraemer KH, Lee MM, Andrews AD, et al. The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch Dermatol. 1994;130(8):1018–21.

    Article  CAS  PubMed  Google Scholar 

  13. Moussaid L, Benchikhi H, Boukind EH, et al. Cutaneous tumors during xeroderma pigmentosum in Morocco: study of 120 patients. Ann Dermatol Venereol. 2004;131(1 Pt 1):29–33.

    Article  CAS  PubMed  Google Scholar 

  14. Messaoud O, Ben Rekaya M, Cherif W, et al. Genetic homogeneity of mutational spectrum of group-A xeroderma pigmentosum in Tunisian patients. Int J Dermatol. 2010;49(5):544–8.

    Article  CAS  PubMed  Google Scholar 

  15. Richards FM, Goudie DR, Cooper WN, et al. Mapping the multiple self-healing squamous epithelioma (MSSE) gene and investigation of xeroderma pigmentosum group A (XPA) and PATCHED (PTCH) as candidate genes. Hum Genet. 1997;101(3):317–22.

    Article  CAS  PubMed  Google Scholar 

  16. Bose S, Morgan LJ, Booth DR, et al. The elusive multiple self-healing squamous epithelioma (MSSE) gene: further mapping, analysis of candidates, and loss of heterozygosity. Oncogene. 2006;25(5):806–12.

    Article  CAS  PubMed  Google Scholar 

  17. Luande J, Henschke CI, Mohammed N. The Tanzanian human albino skin. Natural history. Cancer. 1985;55(8):1823–8.

    Article  CAS  PubMed  Google Scholar 

  18. Morgan NV, Pasha S, Johnson CA, et al. A germline mutation in BLOC1S3/reduced pigmentation causes a novel variant of Hermansky-Pudlak syndrome (HPS8). Am J Hum Genet. 2006;78(1):160–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Ménasché G, Ho CH, Sanal O, et al. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. 2003;112(3):450–6.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Bruckner-Tuderman L. Hereditary skin diseases of anchoring fibrils. J Dermatol Sci. 1999;20(2):122–33.

    Article  CAS  PubMed  Google Scholar 

  21. Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood. 2003;101(3):822–6.

    Article  CAS  PubMed  Google Scholar 

  22. Mehenni Marrone A, Walne A, Tamary H, et al. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood. 2007;110(13):4198–205.

    Article  Google Scholar 

  23. Petkovic M, Dietschy T, Freire R, et al. The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J Cell Sci. 2005;118(Pt 18):4261–9.

    Article  CAS  PubMed  Google Scholar 

  24. Tsuchiya H, Tomita K, Ohno M, et al. Werner’s syndrome combined with quintuplicate malignant tumors: a case report and review of literature data. Jpn J Clin Oncol. 1991;21(2):135–42.

    CAS  PubMed  Google Scholar 

  25. Robertson KD, Jones PA. Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus. Oncogene. 1999;18:3810–20.

    Google Scholar 

  26. Pollock PM, Harper UL, Hansen KS, Yudt LM, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33:19–20.

    Article  CAS  PubMed  Google Scholar 

  27. Bastian BC. Molecular genetics of melanocytic neoplasia: practical applications for diagnosis. Pathology. 2004;36(5):458–61.

    Article  CAS  PubMed  Google Scholar 

  28. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340–6.

    Article  CAS  PubMed  Google Scholar 

  29. Bauer J, Bastian BC. Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool. Dermatol Ther. 2006;19(1):40–9.

    Article  PubMed  Google Scholar 

  30. Kim KB, Eton O, Davis DW, et al. Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer. 2008;99(5):734–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Koh HK, Caruso A, Gage I, et al. Evaluation of melanoma/skin cancer screening in Massachusetts. Preliminary results. Cancer. 1990;65:375–9.

    Article  CAS  PubMed  Google Scholar 

  32. Leidinger P, Keller A, Borries A, Reichrath J, Rass K, Jager SU, et al. High-throughput miRNA profiling of human melanoma blood samples. BMC Cancer. 2010;10:262.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Jalas JR, Vemula S, Bezrookove V, Leboit PE, Simko JP, Bastian BC. Metastatic melanoma with striking adenocarcinomatous differentiation illustrating phenotypic plasticity in melanoma. Am J Surg Pathol. 2011;35(9):1413–8.

    Article  PubMed Central  PubMed  Google Scholar 

  34. 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;338:879–87.

    Article  CAS  PubMed  Google Scholar 

  35. Molven A, Grimstvedt MB, Steine SJ, Harland M, Avril M-F, Hayward NK, et al. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer. 2005;44:10–8.

    Article  CAS  PubMed  Google Scholar 

  36. Box NF, Duffy DL, Chen W, Stark M, Martin NG, Sturm RA, et al. MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. Am J Hum Genet. 2001;69:765–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Davies H, Bignell GR, Cox C, Stephens P, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  CAS  PubMed  Google Scholar 

  38. Brandt A, Sundquist J, Hemminki K. Risk of incident and fatal melanoma in individuals with a family history of incident or fatal melanoma or any cancer. Br J Dermatol. 2011;165(2):342–8.

    Article  CAS  PubMed  Google Scholar 

  39. Olsen CM, Carroll HJ, Whiteman DC. Familial melanoma: a meta-analysis and estimates of attributable fraction. Cancer Epidemiol Biomarkers Prev. 2010;19(1):65–73.

    Article  PubMed  Google Scholar 

  40. Hemminki K, Zhang H, Czene K. Incidence trends and familial risks in invasive and in situ cutaneous melanoma by sun-exposed body sites. Int J Cancer. 2003;104(6):764–71.

    Article  CAS  PubMed  Google Scholar 

  41. Goldstein AM, Chan M, Harland M, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66(20):9818–28.

    Article  CAS  PubMed  Google Scholar 

  42. Greene MH. The genetics of hereditary melanoma and nevi 1998 update. Cancer. 1999;86(11 Suppl):2464–77.

    Article  CAS  PubMed  Google Scholar 

  43. Cho E, Rosner BA, Feskanich D, et al. Risk factors and individual probabilities of melanoma for whites. J Clin Oncol. 2005;23(12):2669–75.

    Article  PubMed  Google Scholar 

  44. Woetmann A, Glue C, Røpke MA, Skov L, Odum N, Queille-Roussel C, et al. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood. 2011;118(22):5891–900.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Jia P, Zhao Z. VarWalker: personalized mutation network analysis of putative cancer genes from next-generation sequencing data. PLoS Comput Biol. 2014;6:10(2).

    Google Scholar 

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Author information

Authors and Affiliations

  1. GGA—Galil Genetic Analysis; Biotechnology Program, Tel Hai College, 3664, Kazerin, 12900, Israel

    Dani Bercovich Ph.D.

  2. Cancer Genetics, The Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

    Inbal Kedar M.S.

Authors
  1. Dani Bercovich Ph.D.
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  2. Inbal Kedar M.S.
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Correspondence to Dani Bercovich Ph.D. .

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Editors and Affiliations

  1. Pathology and Laboratory Medicine, University of Vermont College of Medicine and University of Vermont Medical Center, Burlington, Vermont, USA

    Debra G.B. Leonard

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© 2016 Springer International Publishing Switzerland

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Bercovich, D., Kedar, I. (2016). Hereditary Skin Cancer. In: Leonard, D. (eds) Molecular Pathology in Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-19674-9_27

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  • DOI: https://doi.org/10.1007/978-3-319-19674-9_27

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19673-2

  • Online ISBN: 978-3-319-19674-9

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