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Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity

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Abstract

Approximately 5–10 % of cutaneous melanoma occurs in kindreds with a hereditary predisposition. Mutations in the CDKN2A gene are found to occur in approximately 20–40 % of these kindreds. The first historical mention of what is now called the familial atypical multiple mole melanoma syndrome appears to be from 1820, with more reports throughout the 1950s, 1960s, and later years. In 1991, Lynch and Fusaro described an association between familial multiple mole melanoma and pancreatic cancer and work continues to elucidate the syndrome’s genotypic and phenotypic heterogeneity. Individuals at risk for familial melanoma need periodic screenings. Unfortunately, adequate screening for pancreatic cancer does not currently exist, but pancreatic cancer’s prominence in the hereditary setting will hopefully act as a stimulus for development of novel screening measures.

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References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  PubMed  Google Scholar 

  2. Hansson J (2010) Familial cutaneous melanoma. Adv Exp Med Biol 685:134–145

    Article  CAS  PubMed  Google Scholar 

  3. Cremin C, Blaine SM, Allanson J, Dorman H, Gibbons CA, Honeywell C, Meschino WS, Permaul J, Carroll JC (2010) Gene messenger topic: familial melanoma. Can Fam Phys 56:31. http://www.cfp.ca/content/suppl/2010/01/18/56.1.31.DC1/FamilialMelanoma_ud.pdf. Accessed 5 Jan 2016

  4. Lynch HT, Fusaro RM (1991) Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome. Pancreas 6:127–131

    Article  CAS  PubMed  Google Scholar 

  5. Norris W (1820) Case of fungoid disease. Edinb Med Surg J 16:562–565

    Google Scholar 

  6. Cawley EP (1952) Genetic aspects of malignant melanoma. Arch Derm Syph 65:440–450

    Article  CAS  Google Scholar 

  7. Anderson DE, Smith JL Jr, McBride CM (1967) Hereditary aspects of malignant melanoma. JAMA 200:741–746

    Article  CAS  PubMed  Google Scholar 

  8. Lynch HT, Krush AJ (1968) Heredity and malignant melanoma: implications for early cancer detection. Can Med Assoc J 99:17–21

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lynch HT, Fusaro RM, Pester J, Lynch JF (1980) Familial atypical multiple mole melanoma (FAMMM) syndrome: genetic heterogeneity and malignant melanoma. Br J Cancer 42:58–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lynch HT, Anderson DE, Krush AJ (1968) Heredity and intraocular malignant melanoma. Study of two families and review of forty-five cases. Cancer 21:119–125

    Article  CAS  PubMed  Google Scholar 

  11. Lynch HT, Fusaro RM, Kimberling WJ, Lynch JF, Danes BS (1983) Familial atypical multiple mole-melanoma (FAMMM) syndrome: segregation analysis. J Med Genet 20:342–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lynch HT, Fusaro RM, Pester J, Oosterhuis JA, Went LN, Rumke P, Neering H, Lynch JF (1981) Tumour spectrum in the FAMMM syndrome. Br J Cancer 44:553–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lynch HT, Fusaro RM, Albano WA, Pester J, Kimberling WJ, Lynch JF (1983) Phenotypic variation in the familial atypical multiple mole-melanoma syndrome (FAMMM). J Med Genet 20:25–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, McClure M, Aitken JF, Anderson DE, Bergman W, Frants R, Goldgar DE, Green A, MacLennan R, Martin NG, Meyer LJ, Youl P, Zone JJ, Skolnick MH, Cannon-Albright LA (1994) Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8:23–26

    Article  CAS  PubMed  Google Scholar 

  15. Gruis NA, van der Velden PA, Sandkuijl LA, Prins DE, Weaver-Feldhaus J, Kamb A, Bergman W, Frants RR (1995) Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds. Nat Genet 10:351–353

    Article  CAS  PubMed  Google Scholar 

  16. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE (1994) Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 8:27–32

    Article  CAS  PubMed  Google Scholar 

  17. Vasen HFA, Gruis NA, Frants RR, van der Velden PA, Hille ETM, Bergman W (2000) Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer 87:809–811

    Article  CAS  PubMed  Google Scholar 

  18. Lynch HT, Brand RE, Hogg D, Deters CA, Fusaro RM, Lynch JF, Liu L, Knezetic J, Lassam NJ, Goggins M, Kern S (2002) Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical multiple mole melanoma-pancreatic carcinoma syndrome. Cancer 94:84–96

    Article  CAS  PubMed  Google Scholar 

  19. Potjer TP, van der Stoep N, Houwing-Duistermaat JJ, Konings ICAW, Aalfs CM, van den Akker PC, Ausems MG, Dommering CJ, van der Kolk LE, Maiburg MC, Spruijt L, Wagner A, Vasen HFA, Hes FJ (2015) Pancreatic cancer-associated gene polymorphisms in a nation-wide cohort of p16-Leiden germline mutation carriers; a case-control study. BMC Res Notes 8:264

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pozo L, Naase M, Cerio R, Blanes A, Diaz-Cano SJ (2001) Critical analysis of histologic criteria for grading atypical (dysplastic) melanocytic nevi. Am J Clin Pathol 115:194–204

    Article  CAS  PubMed  Google Scholar 

  21. Haenssle HA, Korpas B, Hansen-Hagge C, Buhl T, Kaune KM, Johnsen S, Rosenberger A, Schön MP, Emmert S (2010) Selection of patients for long-term surveillance with digital dermoscopy by assessment of melanoma risk factors. Arch Dermatol 146:257–264

    Article  PubMed  Google Scholar 

  22. Berwick M, Begg CB, Fine JA, Roush GC, Barnhill RL (1996) Screening for cutaneous melanoma by skin self-examination. J Natl Cancer Inst 88:17–23

    Article  CAS  PubMed  Google Scholar 

  23. Goulart JM, Malvehy J, Puig S, Martin G, Marghoob AA (2011) Dermoscopy in skin self-examination: a useful tool for select patients. Arch Dermatol 147:53–58

    Article  PubMed  Google Scholar 

  24. Shenoy R, Molenda MA, Mostow EN (2014) The introduction of skin self-photography as a supplement to skin self-examination for the detection of skin cancer. J Am Acad Dermatol 70:e15

    Article  PubMed  Google Scholar 

  25. Janda M, Loescher LJ, Soyer P (2013) Enhanced skin self-examination: a novel approach to skin cancer monitoring and follow-up. JAMA Dermatol 149:231–236

    Article  PubMed  Google Scholar 

  26. Vañó-Galván S, Paoli J, Ríos-Busceta L, Jaén P (2015) Skin self-examination using smartphone photography to improve the early diagnosis of melanoma. Actas Dermosifiliogr 106:75–77

    Article  PubMed  Google Scholar 

  27. Lynch HT, Lynch JF, Lanspa SJ (2010) Familial pancreatic cancer. Cancers 2:1861–1883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Funding was also received from the Liz’s Legacy fund through Kicks for a Cure. Dr. Henry Lynch’s work is partially funded through the Charles F. and Mary C. Heider Chair in Cancer Research, which he holds at Creighton University.

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  1. Department of Preventive Medicine, Creighton University, 2500 California Plaza, Omaha, NE, 68178, USA

    Henry T. Lynch & Trudy G. Shaw

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  1. Henry T. Lynch
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  2. Trudy G. Shaw
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Correspondence to Henry T. Lynch.

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Lynch, H.T., Shaw, T.G. Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity. Familial Cancer 15, 487–491 (2016). https://doi.org/10.1007/s10689-016-9888-2

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