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Melanoma, cutaneous malignant, susceptibility to, 10(TPDS3)

MedGen UID:
862913
Concept ID:
C4014476
Finding
Synonyms: LONG TELOMERE SYNDROME, POT1-RELATED; TPDS3; TUMOR PREDISPOSITION SYNDROME 3
 
Gene (location): POT1 (7q31.33)
 
Monarch Initiative: MONDO:0014368
OMIM®: 615848

Disease characteristics

Excerpted from the GeneReview: POT1 Tumor Predisposition
POT1 tumor predisposition (POT1-TPD) is characterized by an increased lifetime risk for multiple cutaneous melanomas, chronic lymphocytic leukemia (CLL), angiosarcoma (particularly cardiac angiosarcomas), and gliomas. Additional cancers (e.g., colorectal cancer, thyroid cancer, breast angiosarcomas) have been reported in individuals with POT1-TPD but with very limited evidence. The age of onset for first primary cutaneous melanoma ranges from 15 to 80 years. The majority of POT1 associated cancers are diagnosed in adulthood. [from GeneReviews]
Authors:
Marie-Louise Henry  |  Jenae Osborne  |  Tobias Else   view full author information

Additional description

From OMIM
Tumor predisposition syndrome-3 (TPDS3) is an autosomal dominant disorder characterized by an increased risk for the development of various types of benign and malignant neoplasms throughout life, with age-dependent penetrance. The age of tumor onset is usually in adulthood, although there is genetic anticipation and childhood onset has been reported. Affected individuals can develop neoplasms involving epithelial, mesenchymal, and neuronal tissues, as well as clonal hematopoietic syndromes, including lymphoid and myeloid cancers. The disorder is associated with elongated telomeres, which likely results in extended cellular longevity and age-associated accumulation of somatic driver mutations in other genes, such as JAK2 (147796). Inheritance of the disorder shows incomplete penetrance (DeBoy et al., 2023). For a discussion of genetic heterogeneity of TPDS, see TPDS1 (614327). For a discussion of genetic heterogeneity of cutaneous malignant melanoma (CMM), see 155600. For a discussion of genetic heterogeneity of glioma, see GLM1 (137800).  http://www.omim.org/entry/615848

Clinical features

From HPO
Melanoma
MedGen UID:
9944
Concept ID:
C0025202
Neoplastic Process
Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.\n\nMelanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.\n\nMost melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).\n\nA large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.

Professional guidelines

PubMed

Tímár J, Ladányi A
Int J Mol Sci 2022 May 11;23(10) doi: 10.3390/ijms23105384. PMID: 35628196Free PMC Article
Serman N, Vranic S, Glibo M, Serman L, Bukvic Mokos Z
Bosn J Basic Med Sci 2022 Sep 16;22(5):673-682. doi: 10.17305/bjbms.2021.7378. PMID: 35465855Free PMC Article
Zhou L, Lu Y, Yang G, Wu J
Tumour Biol 2014 Feb;35(2):1427-32. Epub 2013 Nov 26 doi: 10.1007/s13277-013-1196-y. PMID: 24277375

Recent clinical studies

Etiology

Zhang Y, Lan S, Wu D
Curr Treat Options Oncol 2022 Oct;23(10):1405-1427. Epub 2022 Sep 20 doi: 10.1007/s11864-022-01007-6. PMID: 36125617Free PMC Article
Serman N, Vranic S, Glibo M, Serman L, Bukvic Mokos Z
Bosn J Basic Med Sci 2022 Sep 16;22(5):673-682. doi: 10.17305/bjbms.2021.7378. PMID: 35465855Free PMC Article
Landi MT, Bishop DT, MacGregor S, Machiela MJ, Stratigos AJ, Ghiorzo P, Brossard M, Calista D, Choi J, Fargnoli MC, Zhang T, Rodolfo M, Trower AJ, Menin C, Martinez J, Hadjisavvas A, Song L, Stefanaki I, Scolyer R, Yang R, Goldstein AM, Potrony M, Kypreou KP, Pastorino L, Queirolo P, Pellegrini C, Cattaneo L, Zawistowski M, Gimenez-Xavier P, Rodriguez A, Elefanti L, Manoukian S, Rivoltini L, Smith BH, Loizidou MA, Del Regno L, Massi D, Mandala M, Khosrotehrani K, Akslen LA, Amos CI, Andresen PA, Avril MF, Azizi E, Soyer HP, Bataille V, Dalmasso B, Bowdler LM, Burdon KP, Chen WV, Codd V, Craig JE, Dębniak T, Falchi M, Fang S, Friedman E, Simi S, Galan P, Garcia-Casado Z, Gillanders EM, Gordon S, Green A, Gruis NA, Hansson J, Harland M, Harris J, Helsing P, Henders A, Hočevar M, Höiom V, Hunter D, Ingvar C, Kumar R, Lang J, Lathrop GM, Lee JE, Li X, Lubiński J, Mackie RM, Malt M, Malvehy J, McAloney K, Mohamdi H, Molven A, Moses EK, Neale RE, Novaković S, Nyholt DR, Olsson H, Orr N, Fritsche LG, Puig-Butille JA, Qureshi AA, Radford-Smith GL, Randerson-Moor J, Requena C, Rowe C, Samani NJ, Sanna M, Schadendorf D, Schulze HJ, Simms LA, Smithers M, Song F, Swerdlow AJ, van der Stoep N, Kukutsch NA, Visconti A, Wallace L, Ward SV, Wheeler L, Sturm RA, Hutchinson A, Jones K, Malasky M, Vogt A, Zhou W, Pooley KA, Elder DE, Han J, Hicks B, Hayward NK, Kanetsky PA, Brummett C, Montgomery GW, Olsen CM, Hayward C, Dunning AM, Martin NG, Evangelou E, Mann GJ, Long G, Pharoah PDP, Easton DF, Barrett JH, Cust AE, Abecasis G, Duffy DL, Whiteman DC, Gogas H, De Nicolo A, Tucker MA, Newton-Bishop JA; GenoMEL Consortium; Q-MEGA and QTWIN Investigators; ATHENS Melanoma Study Group; 23andMe; SDH Study Group; IBD Investigators; Essen-Heidelberg Investigators; AMFS Investigators; MelaNostrum Consortium, Peris K, Chanock SJ, Demenais F, Brown KM, Puig S, Nagore E, Shi J, Iles MM, Law MH
Nat Genet 2020 May;52(5):494-504. Epub 2020 Apr 27 doi: 10.1038/s41588-020-0611-8. PMID: 32341527Free PMC Article
Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S, Lynch HT
J Gastrointestin Liver Dis 2017 Jun;26(2):157-163. doi: 10.15403/jgld.2014.1121.262.maj. PMID: 28617886
Belbasis L, Stefanaki I, Stratigos AJ, Evangelou E
J Dermatol Sci 2016 Dec;84(3):330-339. Epub 2016 Sep 13 doi: 10.1016/j.jdermsci.2016.09.003. PMID: 27663092

Diagnosis

Tímár J, Ladányi A
Int J Mol Sci 2022 May 11;23(10) doi: 10.3390/ijms23105384. PMID: 35628196Free PMC Article
Serman N, Vranic S, Glibo M, Serman L, Bukvic Mokos Z
Bosn J Basic Med Sci 2022 Sep 16;22(5):673-682. doi: 10.17305/bjbms.2021.7378. PMID: 35465855Free PMC Article
Yeh I, Jorgenson E, Shen L, Xu M, North JP, Shain AH, Reuss D, Wu H, Robinson WA, Olshen A, von Deimling A, Kwok PY, Bastian BC, Asgari MM
J Natl Cancer Inst 2019 Oct 1;111(10):1068-1077. doi: 10.1093/jnci/djz005. PMID: 30657954Free PMC Article
Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S, Lynch HT
J Gastrointestin Liver Dis 2017 Jun;26(2):157-163. doi: 10.15403/jgld.2014.1121.262.maj. PMID: 28617886
Belbasis L, Stefanaki I, Stratigos AJ, Evangelou E
J Dermatol Sci 2016 Dec;84(3):330-339. Epub 2016 Sep 13 doi: 10.1016/j.jdermsci.2016.09.003. PMID: 27663092

Therapy

Zhang Y, Lan S, Wu D
Curr Treat Options Oncol 2022 Oct;23(10):1405-1427. Epub 2022 Sep 20 doi: 10.1007/s11864-022-01007-6. PMID: 36125617Free PMC Article
Mai JZ, Zhang R, Sargen MR, Little MP, Alexander BH, Tucker MA, Kitahara CM, Cahoon EK
Hum Reprod 2022 May 3;37(5):1059-1068. doi: 10.1093/humrep/deac029. PMID: 35174864Free PMC Article
Law MH, Aoude LG, Duffy DL, Long GV, Johansson PA, Pritchard AL, Khosrotehrani K, Mann GJ, Montgomery GW, Iles MM, Cust AE, Palmer JM; Melanoma GWAS Consortium, Shannon KF, Spillane AJ, Stretch JR, Thompson JF, Saw RPM, Scolyer RA, Martin NG, Hayward NK, MacGregor S
Hum Mol Genet 2020 Oct 10;29(17):2976-2985. doi: 10.1093/hmg/ddaa156. PMID: 32716505Free PMC Article
Belbasis L, Stefanaki I, Stratigos AJ, Evangelou E
J Dermatol Sci 2016 Dec;84(3):330-339. Epub 2016 Sep 13 doi: 10.1016/j.jdermsci.2016.09.003. PMID: 27663092
Fortes C, Mastroeni S, Boffetta P, Antonelli G, Pilla MA, Bottà G, Anzidei P, Venanzetti F
Cancer Causes Control 2013 Oct;24(10):1779-87. Epub 2013 Jul 17 doi: 10.1007/s10552-013-0255-4. PMID: 23860951

Prognosis

Tímár J, Ladányi A
Int J Mol Sci 2022 May 11;23(10) doi: 10.3390/ijms23105384. PMID: 35628196Free PMC Article
Fidalgo F, Torrezan GT, Sá BCS, Barros BDF, Moredo LF, Valieris R, de Souza SJ, Duprat JP, Krepischi ACV, Carraro DM
PLoS One 2022;17(1):e0262419. Epub 2022 Jan 27 doi: 10.1371/journal.pone.0262419. PMID: 35085295Free PMC Article
Torricelli C, Carron J, Carvalho BF, Macedo LT, Rinck-Junior JA, Lima CSP, Lourenço GJ
Melanoma Res 2021 Oct 1;31(5):476-481. doi: 10.1097/CMR.0000000000000763. PMID: 34284461
Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S, Lynch HT
J Gastrointestin Liver Dis 2017 Jun;26(2):157-163. doi: 10.15403/jgld.2014.1121.262.maj. PMID: 28617886
Belbasis L, Stefanaki I, Stratigos AJ, Evangelou E
J Dermatol Sci 2016 Dec;84(3):330-339. Epub 2016 Sep 13 doi: 10.1016/j.jdermsci.2016.09.003. PMID: 27663092

Clinical prediction guides

Tímár J, Ladányi A
Int J Mol Sci 2022 May 11;23(10) doi: 10.3390/ijms23105384. PMID: 35628196Free PMC Article
Fidalgo F, Torrezan GT, Sá BCS, Barros BDF, Moredo LF, Valieris R, de Souza SJ, Duprat JP, Krepischi ACV, Carraro DM
PLoS One 2022;17(1):e0262419. Epub 2022 Jan 27 doi: 10.1371/journal.pone.0262419. PMID: 35085295Free PMC Article
Law MH, Aoude LG, Duffy DL, Long GV, Johansson PA, Pritchard AL, Khosrotehrani K, Mann GJ, Montgomery GW, Iles MM, Cust AE, Palmer JM; Melanoma GWAS Consortium, Shannon KF, Spillane AJ, Stretch JR, Thompson JF, Saw RPM, Scolyer RA, Martin NG, Hayward NK, MacGregor S
Hum Mol Genet 2020 Oct 10;29(17):2976-2985. doi: 10.1093/hmg/ddaa156. PMID: 32716505Free PMC Article
Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S, Lynch HT
J Gastrointestin Liver Dis 2017 Jun;26(2):157-163. doi: 10.15403/jgld.2014.1121.262.maj. PMID: 28617886
Belbasis L, Stefanaki I, Stratigos AJ, Evangelou E
J Dermatol Sci 2016 Dec;84(3):330-339. Epub 2016 Sep 13 doi: 10.1016/j.jdermsci.2016.09.003. PMID: 27663092

Recent systematic reviews

Guhan SM, Artomov M, McCormick S, Njauw C-, Stratigos AJ, Shannon K, Ellisen LW, Tsao H
Sci Rep 2020 Oct 13;10(1):17051. doi: 10.1038/s41598-020-74237-z. PMID: 33051548Free PMC Article

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