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Tumor predisposition syndrome 3(TPDS3)

MedGen UID:
862913
Concept ID:
C4014476
Finding
Synonyms: Glioma susceptibility 9; LONG TELOMERE SYNDROME, POT1-RELATED; Melanoma, cutaneous malignant, susceptibility to, 10; TPDS3
 
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\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.\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).
Desmoid tumor
MedGen UID:
38187
Concept ID:
C0079218
Neoplastic Process
Benign, slow-growing tumors without any metastatic potential. Despite their benign nature, they can damage nearby structures causing organ dysfunction. Histologically they resemble low-grade fibrosarcomas, but they are very locally aggressive and tend to recur even after complete resection. There is a tendency for recurrence in the setting of prior surgery and the most common localisation of these tumors is intraabdominal from smooth muscle cells of the instestine.

Professional guidelines

PubMed

Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962
Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER
Nat Rev Endocrinol 2018 Apr;14(4):229-249. Epub 2018 Jan 29 doi: 10.1038/nrendo.2017.166. PMID: 29377879Free PMC Article
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Recent clinical studies

Etiology

Rebuzzi F, Ulivi P, Tedaldi G
Int J Mol Sci 2023 Jan 21;24(3) doi: 10.3390/ijms24032137. PMID: 36768460Free PMC Article
Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR
Virchows Arch 2023 Jan;482(1):113-130. Epub 2022 Nov 29 doi: 10.1007/s00428-022-03447-9. PMID: 36445482
Huber-Keener KJ
Best Pract Res Clin Obstet Gynaecol 2022 Jun;82:3-11. Epub 2022 Jan 31 doi: 10.1016/j.bpobgyn.2022.01.007. PMID: 35272929
Zhu T, Goodarzi MO
J Clin Endocrinol Metab 2022 Feb 17;107(3):e899-e911. doi: 10.1210/clinem/dgab757. PMID: 34669940Free PMC Article
Azziz R
Obstet Gynecol 2018 Aug;132(2):321-336. doi: 10.1097/AOG.0000000000002698. PMID: 29995717

Diagnosis

Rudelius M, Weinberg OK, Niemeyer CM, Shimamura A, Calvo KR
Virchows Arch 2023 Jan;482(1):113-130. Epub 2022 Nov 29 doi: 10.1007/s00428-022-03447-9. PMID: 36445482
Tamura R
Int J Mol Sci 2021 May 29;22(11) doi: 10.3390/ijms22115850. PMID: 34072574Free PMC Article
Farrugia FA, Charalampopoulos A
Endocr Regul 2019 Jul 1;53(3):191-212. doi: 10.2478/enr-2019-0020. PMID: 31517632
Boone PM, Scott RM, Marciniak SJ, Henske EP, Raby BA
Am J Respir Crit Care Med 2019 Jun 1;199(11):1344-1357. doi: 10.1164/rccm.201807-1212CI. PMID: 30681372Free PMC Article
Azziz R
Obstet Gynecol 2018 Aug;132(2):321-336. doi: 10.1097/AOG.0000000000002698. PMID: 29995717

Therapy

Ilanchezhian M, Varghese DG, Glod JW, Reilly KM, Widemann BC, Pommier Y, Kaplan RN, Del Rivero J
Front Endocrinol (Lausanne) 2022;13:961650. Epub 2022 Oct 31 doi: 10.3389/fendo.2022.961650. PMID: 36387865Free PMC Article
Zhu T, Goodarzi MO
J Clin Endocrinol Metab 2022 Feb 17;107(3):e899-e911. doi: 10.1210/clinem/dgab757. PMID: 34669940Free PMC Article
Tamura R
Int J Mol Sci 2021 May 29;22(11) doi: 10.3390/ijms22115850. PMID: 34072574Free PMC Article
Mimouni NEH, Paiva I, Barbotin AL, Timzoura FE, Plassard D, Le Gras S, Ternier G, Pigny P, Catteau-Jonard S, Simon V, Prevot V, Boutillier AL, Giacobini P
Cell Metab 2021 Mar 2;33(3):513-530.e8. Epub 2021 Feb 3 doi: 10.1016/j.cmet.2021.01.004. PMID: 33539777Free PMC Article
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO)
Ann Rheum Dis 2019 Aug;78(8):1025-1032. Epub 2019 Apr 24 doi: 10.1136/annrheumdis-2019-215048. PMID: 31018962

Prognosis

Ilanchezhian M, Varghese DG, Glod JW, Reilly KM, Widemann BC, Pommier Y, Kaplan RN, Del Rivero J
Front Endocrinol (Lausanne) 2022;13:961650. Epub 2022 Oct 31 doi: 10.3389/fendo.2022.961650. PMID: 36387865Free PMC Article
Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, Limarzi F, Ferro J, Parente P, Fassan M
Pathologica 2020 Sep;112(3):166-185. doi: 10.32074/1591-951X-166. PMID: 33179620Free PMC Article
Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, Weaver MS, Ding L, Mardis ER, Wilson RK, Gajjar A, Ellison DW, Pappo AS, Pui CH, Nichols KE, Downing JR
N Engl J Med 2015 Dec 10;373(24):2336-2346. Epub 2015 Nov 18 doi: 10.1056/NEJMoa1508054. PMID: 26580448Free PMC Article
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Boland CR, Goel A
Gastroenterology 2010 Jun;138(6):2073-2087.e3. doi: 10.1053/j.gastro.2009.12.064. PMID: 20420947Free PMC Article

Clinical prediction guides

Zhu T, Goodarzi MO
J Clin Endocrinol Metab 2022 Feb 17;107(3):e899-e911. doi: 10.1210/clinem/dgab757. PMID: 34669940Free PMC Article
Sahoo SS, Kozyra EJ, Wlodarski MW
Best Pract Res Clin Haematol 2020 Sep;33(3):101197. Epub 2020 Jul 29 doi: 10.1016/j.beha.2020.101197. PMID: 33038986Free PMC Article
Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, Weaver MS, Ding L, Mardis ER, Wilson RK, Gajjar A, Ellison DW, Pappo AS, Pui CH, Nichols KE, Downing JR
N Engl J Med 2015 Dec 10;373(24):2336-2346. Epub 2015 Nov 18 doi: 10.1056/NEJMoa1508054. PMID: 26580448Free PMC Article
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Shiovitz S, Korde LA
Ann Oncol 2015 Jul;26(7):1291-9. Epub 2015 Jan 20 doi: 10.1093/annonc/mdv022. PMID: 25605744Free PMC Article

Recent systematic reviews

Astiazaran-Symonds E, Ney GM, Higgs C, Oba L, Srivastava R, Livinski AA, Rosenberg PS, Stewart DR
Br J Cancer 2023 Jun;128(11):2089-2096. Epub 2023 Mar 25 doi: 10.1038/s41416-023-02229-7. PMID: 36966234Free PMC Article
Machado RA, Popoff DAV, Martelli-Júnior H
Oral Dis 2022 Jul;28(5):1369-1386. Epub 2022 Mar 22 doi: 10.1111/odi.14179. PMID: 35258156
Jongmans MC, Loeffen JL, Waanders E, Hoogerbrugge PM, Ligtenberg MJ, Kuiper RP, Hoogerbrugge N
Eur J Med Genet 2016 Mar;59(3):116-25. Epub 2016 Jan 26 doi: 10.1016/j.ejmg.2016.01.008. PMID: 26825391
Helder-Woolderink JM, Blok EA, Vasen HF, Hollema H, Mourits MJ, De Bock GH
Eur J Cancer 2016 Mar;55:65-73. Epub 2016 Jan 13 doi: 10.1016/j.ejca.2015.12.005. PMID: 26773421
Lauper JM, Krause A, Vaughan TL, Monnat RJ Jr
PLoS One 2013;8(4):e59709. Epub 2013 Apr 1 doi: 10.1371/journal.pone.0059709. PMID: 23573208Free PMC Article

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