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Open Access 01-03-2017

Identification, genetic testing, and management of hereditary melanoma

Authors: Sancy A. Leachman, Olivia M. Lucero, Jone E. Sampson, Pamela Cassidy, William Bruno, Paola Queirolo, Paola Ghiorzo

Published in: Cancer and Metastasis Reviews | Issue 1/2017

Abstract

Several distinct melanoma syndromes have been defined, and genetic tests are available for the associated causative genes. Guidelines for melanoma genetic testing have been published as an informal “rule of twos and threes,” but these guidelines apply to CDKN2A testing and are not intended for the more recently described non-CDKN2A melanoma syndromes. In order to develop an approach for the full spectrum of hereditary melanoma patients, we have separated melanoma syndromes into two types: “melanoma dominant” and “melanoma subordinate.” Syndromes in which melanoma is a predominant cancer type are considered melanoma dominant, although other cancers, such as mesothelioma or pancreatic cancers, may also be observed. These syndromes are associated with defects in CDKN2A, CDK4, BAP1, MITF, and POT1. Melanoma-subordinate syndromes have an increased but lower risk of melanoma than that of other cancer(s) seen in the syndrome, such as breast and ovarian cancer or Cowden syndrome. Many of these melanoma-subordinate syndromes are associated with well-established predisposition genes (e.g., BRCA1/2, PTEN). It is likely that these predisposition genes are responsible for the increased susceptibility to melanoma as well but with lower penetrance than that observed for the dominant cancer(s) in those syndromes. In this review, we describe our extension of the “rule of twos and threes” for melanoma genetic testing. This algorithm incorporates an understanding of the spectrum of cancers and genes seen in association with melanoma to create a more comprehensive and tailored approach to genetic testing.

Ransohoff, K. J., Jaju, P. D., Tang, J. Y., Carbone, M., Leachman, S., & Sarin, K. Y. (2016). Familial skin cancer syndromes increased melanoma risk. Journal of the American Academy of Dermatology, 74(3), 423–434. doi:10.1016/j.jaad.2015.09.070.CrossRefPubMed

Read, J., Wadt, K. A. W., & Hayward, N. K. (2015). Melanoma genetics. Journal of Medical Genetics, 53, 1–14. doi:10.1136/jmedgenet-2015-103150.CrossRefPubMed

Goldstein, A. M., Chan, M., Harland, M., Hayward, N. K., Demenais, F., Bishop, D. T., et al. (2007). Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. Journal of Medical Genetics, 44(2), 99–106. doi:10.1136/jmg.2006.043802.CrossRefPubMed

Taber, J. M., Aspinwall, L. G., Stump, T. K., Kohlmann, W., Champine, M., & Leachman, S. A. (2015). Genetic test reporting enhances understanding of risk information and acceptance of prevention recommendations compared to family history-based counseling alone. Journal of Behavioral Medicine, 38(5), 740–753. doi:10.1007/s10865-015-9648-z.CrossRefPubMedPubMedCentral

Aspinwall, L. G., Taber, J. M., Kohlmann, W., Leaf, S. L., & Leachman, S. A. (2014). Unaffected family members report improvements in daily routine sun-protection 2 years following melanoma genetic testing. Genetics in Medicine, 16, 356–372. doi:10.1007/s12671-013-0269-8.Moving.CrossRef

Goldstein, A. M., Chan, M., Harland, M., Gillanders, E. M., Hayward, N. K., Avril, M. F., et al. (2006). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Research, 66(20), 9818–9828. doi:10.1158/0008-5472.CAN-06-0494.CrossRefPubMed

Eliason, M. J., Larson, A. A., Florell, S. R., Zone, J. J., Cannon-Albright, L. A., Samlowski, W. E., & Leachman, S. A. (2006). Population-based prevalence of CDKN2A mutations in Utah melanoma families. The Journal of Investigative Dermatology, 126(3), 660–666. doi:10.1038/sj.jid.5700094.CrossRefPubMed

Hussussian, C. J., Struewing, J. P., Goldstein, A. M., Higgins, P. A., Ally, D. S., Sheahan, M. D., et al. (1994). Germline p16 mutations in familial melanoma. Nature Genetics, 8, 15–21. doi:10.1038/ng0994-15.CrossRefPubMed

Kamb, A., Shattuck-Eidens, D., Eeles, R., Liu, Q., Gruis, N. A., Ding, W., et al. (1994). Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nature Genetics, 8(1), 22–26. doi:10.1038/ng0994-22.CrossRef

10.

Zhang, Y., Xiong, Y., & Yarbrough, W. G. (1998). ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell, 92(6), 725–734. doi:10.1016/S0092-8674(00)81401-4.CrossRefPubMed

11.

Goldstein, A. M. (2004). Familial melanoma, pancreatic cancer and germline CDKN2A mutations. Human Mutation, 23(September 2003), 630. doi:10.1002/humu.9247.CrossRefPubMed

12.

Vasen, H. F. A., Gruis, N. A., Frants, R. R., Van Der Velden, P. A., Hille, E. T. M., & 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). International Journal of Cancer, 87(6), 809–811. doi:10.1002/1097-0215(20000915)87:6<809::AID-IJC8>3.0.CO;2-U.CrossRefPubMed

13.

Lynch, H. T., & Shaw, T. G. (2016). Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity. Familial Cancer, 15(3), 487–491. doi:10.1007/s10689-016-9888-2.CrossRefPubMed

14.

Yang, X. R., Rotunno, M., Xiao, Y., Ingvar, C., Helgadottir, H., Pastorino, L., et al. (2016). Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations. Human Genetics, 135(11), 1241–1249. doi:10.1007/s00439-016-1715-1.CrossRefPubMed

15.

Soura, E., Eliades, P. J., Shannon, K., Stratigos, A. J., & Tsao, H. (2016). Hereditary melanoma: update on syndromes and management genetics of familial atypical multiple mole melanoma syndrome. Journal of the American Academy of Dermatology, 74(3), 411–420. doi:10.1016/j.jaad.2015.08.038.CrossRefPubMedPubMedCentral

16.

Borg, A., Sandberg, T., Nilsson, K., Johannsson, O., Klinker, M., Måsbäck, A., et al. (2000). High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. Journal of the National Cancer Institute, 92(15), 1260–1266.CrossRefPubMed

17.

Ghiorzo, P., Fornarini, G., Sciallero, S., Battistuzzi, L., Belli, F., Bernard, L., et al. (2012). CDKN2A is the main susceptibility gene in Italian pancreatic cancer families. Journal of Medical Genetics, 49(3), 164–170. doi:10.1136/jmedgenet-2011-100281.CrossRefPubMed

18.

Ghiorzo, P. (2014). Genetic predisposition to pancreatic cancer. World Journal of Gastroenterology, 20(31), 10778. doi:10.3748/wjg.v20.i31.10778.CrossRefPubMedPubMedCentral

19.

Leachman, S. A., Carucci, J., Kohlmann, W., Banks, K. C., Asgari, M. M., Bergman, W., et al. (2009). Selection criteria for genetic assessment of patients with familial melanoma. Journal of the American Academy of Dermatology, 61(4), 677.e1–677.14. doi:10.1016/j.jaad.2009.03.016.CrossRefPubMed

20.

Bahuau, M., Vidaud, D., Jenkins, R. B., Bièche, I., Kimmel, D. W., Assouline, B., et al. (1998). Germ-line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumors. Cancer Research, 58(11), 2298–2303.PubMed

21.

Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., Walker, G. J., et al. (1996). Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nature Genetics, 12, 97–99. doi:10.1038/ng0196-97.CrossRefPubMed

22.

Soufir, N. (1998). Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group [published erratum appears in Hum Mol Genet 1998 May;7(5):941]. Human Molecular Genetics, 7(2), 209–216. doi:10.1093/hmg/7.2.209

23.

Puntervoll, H. E., Yang, X. R., Vetti, H. H., Bachmann, I. M., Avril, M. F., Benfodda, M., et al. (2013). Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants. Journal of Medical Genetics, 50(4), 264–270. doi:10.1136/jmedgenet-2012-101455.CrossRefPubMedPubMedCentral

24.

Horn, S., Figl, A., Rachakonda, P. S., Fischer, C., Sucker, A., Gast, A., et al. (2013). TERT promoter mutations in familial and sporadic melanoma. Science, 339(6122), 959–961. doi:10.1126/science.1230062.CrossRefPubMed

25.

Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A. (2013). Highly recurrent TERT promoter mutations in human melanoma. Science, 339(6122), 957–959. doi:10.1126/science.1229259.CrossRefPubMedPubMedCentral

26.

Shi, J., Yang, X. R., Ballew, B., Rotunno, M., Calista, D., Fargnoli, M. C., et al. (2014). Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nature Genetics, 46(5), 482–486. doi:10.1038/ng.2941.CrossRefPubMedPubMedCentral

27.

Robles-Espinoza, C. D., Harland, M., Ramsay, A. J., Aoude, L. G., Quesada, V., Ding, Z., et al. (2014). POT1 loss-of-function variants predispose to familial melanoma. Nature Genetics, 46(5), 478–481. doi:10.1038/ng.2947.CrossRefPubMedPubMedCentral

28.

Aoude, L. G., Pritchard, A. L., Robles-Espinoza, C. D., Wadt, K., Harland, M., Choi, J., et al. (2014). Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma. JNCI Journal of the National Cancer Institute, 107(2), dju408. doi:10.1093/jnci/dju408.CrossRefPubMedPubMedCentral

29.

Harbour, J. W., Onken, M. D., Roberson, E. D. O., Duan, S., Cao, L., Worley, L. A., et al. (2010). Frequent mutation of BAP1 in metastasizing uveal melanomas. Science (New York, N.Y.), 330(6009), 1410–1413. doi:10.1126/science.1194472.CrossRef

30.

Wiesner, T., Obenauf, A. C., Murali, R., Fried, I., Griewank, K. G., Ulz, P., et al. (2011). Germline mutations in BAP1 predispose to melanocytic tumors. Nature Genetics, 43(10), 1018–1021. doi:10.1038/ng.910.CrossRefPubMedPubMedCentral

31.

Testa, J. R., Cheung, M., Pei, J., Below, J. E., Tan, Y., Sementino, E., et al. (2011). Germline BAP1 mutations predispose to malignant mesothelioma. Nature Genetics, 43(10), 1022–1025. doi:10.1038/ng.912.CrossRefPubMedPubMedCentral

32.

Abdel-Rahman, M. H., Pilarski, R., Cebulla, C. M., Massengill, J. B., Christopher, B. N., Boru, G., et al. (2011). Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. Journal of Medical Genetics, 48(12), 856–859. doi:10.1136/jmedgenet-2011-100156.CrossRefPubMed

33.

Wang, A., Papneja, A., Hyrcza, M., Al-Habeeb, A., & Ghazarian, D. (2016). Gene of the month: BAP1. Journal of Clinical Pathology, 69(9), 750–753. doi:10.1136/jclinpath-2016-203866.CrossRefPubMed

34.

Rai, K., Pilarski, R., Cebulla, C. M., & Abdel-Rahman, M. H. (2016). Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clinical Genetics, 89(3), 285–294. doi:10.1111/cge.12630.CrossRefPubMed

35.

Bertolotto, C., Lesueur, F., Giuliano, S., Strub, T., de Lichy, M., Bille, K., et al. (2011). A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature, 480(7375), 94–98. doi:10.1038/nature10539.CrossRefPubMed

36.

Yokoyama, S., Woods, S. L., Boyle, G. M., Aoude, L. G., MacGregor, S., Zismann, V., et al. (2011). A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature, 480(7375), 99–103. doi:10.1038/nature10630.CrossRefPubMedPubMedCentral

37.

Ghiorzo, P., Pastorino, L., Queirolo, P., Bruno, W., Tibiletti, M. G., Nasti, S., et al. (2013). Prevalence of the E318K MITF germline mutation in Italian melanoma patients: associations with histological subtypes and family cancer history. Pigment Cell & Melanoma Research, 26(2), 259–262. doi:10.1111/pcmr.12047.CrossRef

38.

Mangas, C., Potrony, M., Mainetti, C., Bianchi, E., Carrozza Merlani, P., Mancarella Eberhardt, A., et al. (2016). Genetic susceptibility to cutaneous melanoma in southern Switzerland: role of CDKN2A, MC1R and MITF. British Journal of Dermatology, 175(5), 1030–1037. doi:10.1111/bjd.14897.CrossRefPubMed

39.

Castro-Vega, L. J., Kiando, S. R., Burnichon, N., Buffet, A., Amar, L., Simian, C., et al. (2016). The MITF, p.E318K variant as a risk factor for pheochromocytoma and paraganglioma. The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/jc.2016-2103.

40.

Molven, A., Grimstvedt, M. B., Steine, S. J., Harland, M., Avril, M.-F., Hayward, N. K., & Akslen, L. A. (2005). A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, andCDK4 mutation. Genes, Chromosomes and Cancer, 44(1), 10–18. doi:10.1002/gcc.20202.CrossRefPubMed

41.

Tang, J., & Chu, G. (2002). Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein. DNA Repair, 1(8), 601–616.CrossRefPubMedPubMedCentral

42.

Tan, M.-H., Mester, J. L., Ngeow, J., Rybicki, L. A., Orloff, M. S., & Eng, C. (2012). Lifetime cancer risks in individuals with germline PTEN mutations. Clinical Cancer Research, 18(2), 400–407. doi:10.1158/1078-0432.CCR-11-2283.CrossRefPubMedPubMedCentral

43.

Pötzsch, C., Voigtländer, T., & Lübbert, M. (2002). p53 germline mutation in a patient with Li-Fraumeni syndrome and three metachronous malignancies. Journal of Cancer Research and Clinical Oncology, 128(8), 456–460. doi:10.1007/s00432-002-0360-3.CrossRefPubMed

44.

Bruno, W., Ghiorzo, P., Battistuzzi, L., Ascierto, P. A., Barile, M., Gargiulo, S., et al. (2009). Clinical genetic testing for familial melanoma in Italy: a cooperative study. Journal of the American Academy of Dermatology, 61(5), 775–782. doi:10.1016/j.jaad.2009.03.039.CrossRefPubMed

45.

Bruno, W., Pastorino, L., Ghiorzo, P., Andreotti, V., Martinuzzi, C., Menin, C., et al. (2016). Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup. Journal of the American Academy of Dermatology, 74(2), 325–332. doi:10.1016/j.jaad.2015.09.053.CrossRefPubMed

46.

Cancer of the Breast (Female) - SEER Stat Fact Sheets. (n.d.). Retrieved from https://seer.cancer.gov/statfacts/html/breast.html.

47.

Kraemer, K. H., & DiGiovanna, J. J. (1993). Xeroderma pigmentosum, GeneReviews(®). Seattle: University of Washington.

48.

Pande, M., Wei, C., Chen, J., Amos, C. I., Lynch, P. M., Lu, K. H., et al. (2012). Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry. Familial Cancer, 11(3), 441–447. doi:10.1007/s10689-012-9534-6.CrossRefPubMedPubMedCentral

49.

Eng, C. (1993). PTEN hamartoma tumor syndrome. 2001 Nov 29 [Updated 2016 Jun 2]. In: PagonRA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1488/

50.

Genomic Medicine Institute - PTEN Cleveland Clinic Score Calculator for Estimation of PTEN Mutation Probability (n.d.). Retrieved January 4, 2017, from https://www.lerner.ccf.org/gmi/ccscore/documents/adult_criteria.php.

51.

Tan, M.-H., Mester, J., Peterson, C., Yang, Y., Chen, J.-L., Rybicki, L. A., et al. (2011). A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. American Journal of Human Genetics, 88(1), 42–56. doi:10.1016/j.ajhg.2010.11.013.CrossRefPubMedPubMedCentral

52.

Schneider, K., Zelley, K., Nichols, K. E., & Garber, J. (1993). Li-Fraumeni syndrome, GeneReviews(®). Seattle: University of Washington.

53.

Pilarski, R., Buys, S. S., Farmer, M., Friedman, S., Garber, J. E., Dana-Farber, M., … Dwyer, M. (n.d.). NCCN guidelines version 1.2017 panel members genetic/familial high-risk assessment: breast and ovarian DVM ¥ FORCE: facing our risk of cancer empowered.

54.

Bancroft, E. K., Page, E. C., Castro, E., Lilja, H., Vickers, A., Sjoberg, D., et al. (2014). Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. European Urology, 66(3), 489–499. doi:10.1016/j.eururo.2014.01.003.CrossRefPubMedPubMedCentral

55.

Carroll, P. R., Parsons, J. K., Andriole, G., Bahnson, R. R., Castle, E. P., Catalona, W. J., et al. (2016). NCCN guidelines insights: prostate cancer early detection, version 2.2016. Journal of the National Comprehensive Cancer Network : JNCCN, 14(5), 509–519.PubMed

56.

Susan Darlow, N., Dwyer, M., Gupta, S., Ahnen, D. J., Bray, T., Cooper, G., … Weinberg, D. (n.d.). NCCN guidelines version 2.2016 panel members colorectal cancer screening.

57.

Jasperson, K. W., & Burt, R. W. (1993). APC-associated polyposis conditions, GeneReviews(®). Seattle: University of Washington.

58.

Canto, M. I., Harinck, F., Hruban, R. H., Offerhaus, G. J., Poley, J.-W., Kamel, I., et al. (2013). International Cancer of the Pancreas Screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 62(3), 339–347. doi:10.1136/gutjnl-2012-303108.CrossRefPubMed

59.

Raskind, W. H., Hisama, F. M., & Bennett, R. L. (2016). Biochemical and imaging surveillance in Li-Fraumeni syndrome. The Lancet Oncology, 17(11), e472. doi:10.1016/S1470-2045(16)30530-7.CrossRefPubMed

60.

Solomon, S., Das, S., Brand, R., & Whitcomb, D. C. (2012). Inherited pancreatic cancer syndromes. The Cancer Journal, 18(6), 485–491. doi:10.1097/PPO.0b013e318278c4a6.CrossRefPubMedPubMedCentral

61.

Ahmed, M., & Rahman, N. (2006). ATM and breast cancer susceptibility. Oncogene, 25(43), 5906–5911. doi:10.1038/sj.onc.1209873.CrossRefPubMed

62.

Lammi, L., Arte, S., Somer, M., Järvinen, H., Lahermo, P., Thesleff, I., et al. (2004). Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. The American Journal of Human Genetics, 74(5), 1043–1050. doi:10.1086/386293.CrossRefPubMed

63.

Ratajska, M., Antoszewska, E., Piskorz, A., Brozek, I., Borg, Å., Kusmierek, H., et al. (2012). Cancer predisposing BARD1 mutations in breast–ovarian cancer families. Breast Cancer Research and Treatment, 131(1), 89–97. doi:10.1007/s10549-011-1403-8.CrossRefPubMed

64.

Larsen Haidle, J., & Howe, J. R. (1993). Juvenile polyposis syndrome, GeneReviews(®). Seattle: University of Washington.

65.

Hall, M. J., Reid, J. E., Burbidge, L. A., Pruss, D., Deffenbaugh, A. M., Frye, C., et al. (2009). BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer, 115(10), 2222–2233. doi:10.1002/cncr.24200.CrossRefPubMedPubMedCentral

66.

Liede, A., Karlan, B. Y., & Narod, S. A. (2004). Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. Journal of Clinical Oncology. doi:10.1200/JCO.2004.05.055.PubMed

67.

Rafnar, T., Gudbjartsson, D. F., Sulem, P., Jonasdottir, A., Sigurdsson, A., Jonasdottir, A., et al. (2011). Mutations in BRIP1 confer high risk of ovarian cancer. Nature Genetics, 43(11), 1104–1107. doi:10.1038/ng.955.CrossRefPubMed

68.

Hansford, S., Kaurah, P., Li-Chang, H., Woo, M., Senz, J., Pinheiro, H., et al. (2015). Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncology, 1(1), 23–32. doi:10.1001/jamaoncol.2014.168.CrossRefPubMed

69.

van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., et al. (2015). Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. Journal of Medical Genetics, 52(6), 361–374. doi:10.1136/jmedgenet-2015-103094.CrossRefPubMedPubMedCentral

70.

Weischer, M., Bojesen, S. E., Ellervik, C., Tybjærg-Hansen, A., & Nordestgaard, B. G. (2008). CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. Journal of Clinical Oncology, 26(4), 542–548. doi:10.1200/JCO.2007.12.5922.CrossRefPubMed

71.

Cybulski, C., Wokołorczyk, D., Huzarski, T., Byrski, T., Gronwald, J., Górski, B., et al. (2006). A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer. Journal of Medical Genetics, 43(11), 863–866. doi:10.1136/jmg.2006.044974.CrossRefPubMedPubMedCentral

72.

Xiang, H., Geng, X., Ge, W., & Li, H. (2011). Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. European Journal of Cancer, 47(17), 2546–2551. doi:10.1016/j.ejca.2011.03.025.CrossRefPubMed

73.

Schultz, K. A. P., Pacheco, M. C., Yang, J., Williams, G. M., Messinger, Y., Hill, D. A., et al. (2011). Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the international pleuropulmonary blastoma registry. Gynecologic Oncology, 122(2), 246–250. doi:10.1016/j.ygyno.2011.03.024.CrossRefPubMedPubMedCentral

74.

Kempers, M. J., Kuiper, R. P., Ockeloen, C. W., Chappuis, P. O., Hutter, P., Rahner, N., et al. (2011). High colorectal and low endometrial cancer risk in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncology, 12(1), 49–55. doi:10.1016/S1470-2045(10)70265-5.CrossRefPubMed

75.

Bellam, N., & Pasche, B. (2010). Tgf-beta signaling alterations and colon cancer. Cancer treatment and research. doi:10.1007/978-1-4419-6033-7_5.PubMed

76.

Cai, Q., Wang, X., Li, X., Gong, R., Guo, X., Tang, Y., et al. (2015). Germline HOXB13 p.Gly84Glu mutation and cancer susceptibility: a pooled analysis of 25 epidemiological studies with 145,257 participates. Oncotarget, 5(39). doi:10.18632/oncotarget.5994.

77.

Falchetti, A., Marini, F., Luzi, E., Giusti, F., Cavalli, L., Cavalli, T., & Brandi, M. L. (2009). Multiple endocrine neoplasia type 1 (MEN1): not only inherited endocrine tumors. Genetics in medicine : official journal of the American College of Medical Genetics, 11(12), 825–835. doi:10.1097/GIM.0b013e3181be5c97.CrossRef

78.

Dominguez-Valentin, M., Joost, P., Therkildsen, C., Jonsson, M., Rambech, E., & Nilbert, M. (2016). Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urology, 16(1), 15. doi:10.1186/s12894-016-0130-1.CrossRefPubMedPubMedCentral

79.

Kohlmann, W., & Gruber, S. B. (1993). Lynch syndrome, GeneReviews(®). Seattle: University of Washington.

80.

Bonadona, V., Bonaiti, B., Grandjouan, S., Huiart, L., Caron, O., Colas, C., & Bonaı, C. (2011). Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. The Journal of the American Medical Association, 305(22), 2304–2310. doi:10.1001/jama.2011.743.CrossRefPubMed

81.

Win, A. K., Dowty, J. G., Cleary, S. P., Kim, H., Buchanan, D. D., Young, J. P., … Jenkins, M. A. (2014). Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family HISTORY of cancer. Gastroenterology.

82.

Zhang, B., Beeghly-Fadiel, A., Long, J., & Zheng, W. (2011). Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. The Lancet Oncology, 12(5), 477–488. doi:10.1016/S1470-2045(11)70076-6.CrossRefPubMedPubMedCentral

83.

Cybulski, C., Gorski, B., Debniak, T., Gliniewicz, B., Mierzejewski, M., Masojc, B., et al. (2004). NBS1 is a prostate cancer susceptibility gene. Cancer Research, 64(4), 1215–1219.CrossRefPubMed

84.

Graffeo, R., Livraghi, L., Pagani, O., Goldhirsch, A., Partridge, A. H., & Garber, J. E. (2016). Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care. Breast Cancer Research and Treatment, 160(3), 393–410. doi:10.1007/s10549-016-4003-9.CrossRefPubMed

85.

Kanchi, K.L., Johnson, K.J., Lu, C., McLellan, M.D., Leiserson, M.D.M., Wendl, M.C., … Ding, L. (2014). Integrated analysis of germline and somatic variants in ovarian cancer. Nature Communications, 5. doi:10.1038/ncomms4156

86.

Antoniou, A. C., Casadei, S., Heikkinen, T., Barrowdale, D., Pylkäs, K., Roberts, J., et al. (2014). Breast-cancer risk in families with mutations in PALB2. The New England Journal of Medicine, 371(6), 497–506. doi:10.1056/NEJMoa1400382.CrossRefPubMedPubMedCentral

87.

Bellido, F., Pineda, M., Aiza, G., Valdés-Mas, R., Navarro, M., Puente, D. A., et al. (2016). POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. Genetics in Medicine, 18(4), 325–332. doi:10.1038/gim.2015.75.CrossRefPubMed

88.

Damiola, F., Pertesi, M., Oliver, J., Le Calvez-Kelm, F., Voegele, C., Young, E. L., et al. (2014). Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study. Breast Cancer Research, 16(3), R58. doi:10.1186/bcr3669.CrossRefPubMedPubMedCentral

89.

Minion, L. E., Dolinsky, J. S., Chase, D. M., Dunlop, C. L., Chao, E. C., & Monk, B. J. (2015). Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2. Gynecologic Oncology, 137(1), 86–92. doi:10.1016/j.ygyno.2015.01.537.CrossRefPubMed

90.

Loveday, C., Turnbull, C., Ruark, E., Xicola, R. M. M., Ramsay, E., Hughes, D., et al. (2012). Germline RAD51C mutations confer susceptibility to ovarian cancer. Nature Genetics, 44(5), 475–476. doi:10.1038/ng.2224.CrossRefPubMed

91.

Thompson, E. R., Rowley, S. M., Sawyer, S., kConFab, Eccles, D. M., Trainer, A. H., et al. (2013). Analysis of RAD51D in ovarian cancer patients and families with a history of ovarian or breast cancer. PloS One, 8(1), e54772. doi:10.1371/journal.pone.0054772.CrossRefPubMedPubMedCentral

92.

Foulkes, W. D., Clarke, B. A., Hasselblatt, M., Majewski, J., Albrecht, S., & McCluggage, W. G. (2014). No small surprise—small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour. The Journal of Pathology, 233(3), 209–214. doi:10.1002/path.4362.CrossRefPubMed

93.

van Lier, M. G. F., Wagner, A., Mathus-Vliegen, E. M. H., Kuipers, E. J., Steyerberg, E. W., & van Leerdam, M. E. (2010). High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. The American Journal of Gastroenterology, 105(6), 1258–1264 author reply 1265. doi:10.1038/ajg.2009.725.CrossRefPubMed

94.

Olivier, M., Goldgar, D. E., Sodha, N., Ohgaki, H., Kleihues, P., Hainaut, P., & Eeles, R. A. (2003). Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Research, 63(20), 6643–6650.PubMed

95.

Bougeard, G., Renaux-Petel, M., Flaman, J.-M., Charbonnier, C., Fermey, P., Belotti, M., et al. (2015). Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. Journal of Clinical Oncology, 33(21), 2345–2352. doi:10.1200/JCO.2014.59.5728.CrossRefPubMed

96.

Arva, N. C., Pappas, J. G., Bhatla, T., Raetz, E. A., Macari, M., Ginsburg, H. B., & Hajdu, C. H. (2012). Well-differentiated pancreatic neuroendocrine carcinoma in tuberous sclerosis—case report and review of the literature. The American Journal of Surgical Pathology, 36(1), 149–153. doi:10.1097/PAS.0b013e31823d0560.CrossRefPubMed

97.

Keutgen, X. M., Hammel, P., Choyke, P. L., Libutti, S. K., Jonasch, E., & Kebebew, E. (2016). Evaluation and management of pancreatic lesions in patients with von Hippel–Lindau disease. Nature Reviews Clinical Oncology, 13(9), 537–549. doi:10.1038/nrclinonc.2016.37.CrossRefPubMed

Title: Identification, genetic testing, and management of hereditary melanoma
Authors: Sancy A. Leachman
Olivia M. Lucero
Jone E. Sampson
Pamela Cassidy
William Bruno
Paola Queirolo
Paola Ghiorzo
Publication date: 01-03-2017
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1/2017
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-017-9661-5

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