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BAP1-related tumor predisposition syndrome(TPDS1)

MedGen UID:
482122
Concept ID:
C3280492
Disease or Syndrome
Synonyms: BAP1 tumor predisposition syndrome; COMMON Syndrome; TPDS1; Tumor predisposition syndrome; TUMOR PREDISPOSITION SYNDROME 1; Tumor susceptibility linked to germline BAP1 mutations
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): BAP1 (3p21.1)
 
Monarch Initiative: MONDO:0013692
OMIM®: 614327
Orphanet: ORPHA289539

Disease characteristics

Excerpted from the GeneReview: BAP1 Tumor Predisposition Syndrome
BAP1 tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for a specific skin lesion, BAP1-inactivated melanocytic tumors (BIMT; formerly called atypical Spitz tumors), and the following cancers, in descending order of frequency: uveal (eye) melanoma (UM), malignant mesothelioma (MMe), cutaneous melanoma (CM), renal cell carcinoma (RCC), and basal cell carcinoma (BCC). Hepatocellular carcinoma, cholangiocarcinoma, and meningioma may also be associated with BAP1-TPDS. Affected individuals can have more than one type of primary cancer. In general, the median age of onset of these tumors is younger than in the general population. UM tends to be a more aggressive class 2 tumor with higher risk for metastasis and reduced survival compared to UM occurring in the general population. Due to the limited number of families reported to date, the penetrance, natural history, and frequencies of BAP1-associated tumors are yet to be determined. Other suspected but unconfirmed tumors in BAP1-TPDS include (in alphabetic order): breast cancer, neuroendocrine carcinoma, non-small-cell lung adenocarcinoma, thyroid cancer, and urinary bladder cancer. [from GeneReviews]
Authors:
Robert Pilarski  |  Maria I Carlo  |  Colleen Cebulla, et. al.   view full author information

Additional descriptions

From OMIM
Tumor predisposition syndrome-1 (TPDS1) is inherited in an autosomal dominant pattern. Individuals carrying heterozygous BAP1 mutations are at high-risk for the development of a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma (155720), cutaneous melanoma (155600), malignant mesothelioma on exposure to asbestos (156240), and other cancer types, such as lung adenocarcinoma, meningioma, and renal cell carcinoma (summary by Wiesner et al., 2011, Testa et al., 2011, Abdel-Rahman et al., 2011, and Popova et al., 2013). Genetic Heterogeneity of Tumor Predisposition Syndrome See also TPDS2 (619975), caused by mutation in the MBD4 gene (603574) on chromosome 3q21; TPDS3 (615848), caused by mutation in the POT1 gene (606478) on chromosome 7q31; and TPDS4 (609265), caused by mutation in the CHEK2 gene (604373) on chromosome 22q12.  http://www.omim.org/entry/614327
From MedlinePlus Genetics
BAP1 tumor predisposition syndrome is an inherited disorder that increases the risk of a variety of cancerous (malignant) and noncancerous (benign) tumors, most commonly certain types of tumors that occur in the skin, eyes, kidneys, and the tissue that lines the chest, abdomen, and the outer surface of the internal organs (the mesothelium). Affected individuals can develop one or more types of tumor, and affected members of the same family can have different types.

Some people with BAP1 tumor predisposition syndrome develop growths in the skin known as atypical Spitz tumors. People with this syndrome may have more than one of these tumors, and they can have dozens. Atypical Spitz tumors are generally considered benign, although it is unclear if they can become cancerous. Skin cancers are also associated with BAP1 tumor predisposition syndrome, including cutaneous melanoma and basal cell carcinoma.

A type of eye cancer called uveal melanoma is the most common cancerous tumor in BAP1 tumor predisposition syndrome. Although uveal melanoma does not usually cause any symptoms, some people with this type of cancer have blurred vision; small, moving dots (floaters) or flashes of light in their vision; headaches; or a visible dark spot on the eye.

People with BAP1 tumor predisposition syndrome are at risk of developing malignant mesothelioma, which is cancer of the mesothelium. When associated with BAP1 tumor predisposition syndrome, malignant mesothelioma most often occurs in the membrane that lines the abdomen and covers the abdominal organs (the peritoneum). It less commonly occurs in the outer covering of the lungs (the pleura).

A form of kidney cancer called clear cell renal cell carcinoma is also associated with the condition. Researchers are still determining whether other forms of cancer are linked to BAP1 tumor predisposition syndrome.

When they occur in people with BAP1 tumor predisposition syndrome, cancers tend to arise at a younger age and are often more aggressive than cancers in the general population. The cancerous tumors in BAP1 tumor predisposition syndrome tend to spread (metastasize) to other parts of the body. Survival of affected individuals with this syndrome is usually shorter than in other people who have one of these cancers. However, individuals with malignant mesothelioma as part of the BAP1 tumor predisposition syndrome appear to survive longer than those who have the cancer without the syndrome.  https://medlineplus.gov/genetics/condition/bap1-tumor-predisposition-syndrome

Clinical features

From HPO
Renal cell carcinoma
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
A type of carcinoma of the kidney with origin in the epithelium of the proximal convoluted renal tubule.
Malignant melanoma of skin
MedGen UID:
57486
Concept ID:
C0151779
Neoplastic Process
A 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).\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\nMelanoma 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.
Lung adenocarcinoma
MedGen UID:
57744
Concept ID:
C0152013
Neoplastic Process
A carcinoma that arises from the lung and is characterized by the presence of malignant glandular epithelial cells. There is a male predilection with a male to female ratio of 2:1. Usually lung adenocarcinoma is asymptomatic and is identified through screening studies or as an incidental radiologic finding. If clinical symptoms are present they include shortness of breath, cough, hemoptysis, chest pain, and fever. Tobacco smoke is a known risk factor.
Mesothelioma, malignant
MedGen UID:
91062
Concept ID:
C0345967
Neoplastic Process
Malignant mesothelioma is an aggressive neoplasm of the serosal lining of the chest etiologically linked to asbestos. It is diagnosed in approximately 2,000 to 3,000 individuals annually in the United States, most of whom die within 2 years of diagnosis (summary by Bott et al., 2011). See also 614327 for a tumor predisposition syndrome that may contribute to the development of malignant mesothelioma upon asbestos exposure and is caused by germline mutation in the BAP1 gene (603089) on chromosome 3p21.
Meningioma
MedGen UID:
7532
Concept ID:
C0025286
Neoplastic Process
The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater.
Uveal melanoma
MedGen UID:
65077
Concept ID:
C0220633
Neoplastic Process
Uveal melanoma is a highly malignant tumor that arises from the choroid or the ciliary body of the eye. It is the most common primary ocular malignancy in adults, although it has a low incidence (6 cases per 1,000,000 per year). A tendency for hematogenic spread to the liver accounts for up to 50% of patient deaths (summary by Lopez et al., 2007).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBAP1-related tumor predisposition syndrome
Follow this link to review classifications for BAP1-related tumor predisposition syndrome in Orphanet.

Recent clinical studies

Etiology

Pagliuca F, Zito Marino F, Morgillo F, Della Corte C, Santini M, Vicidomini G, Guggino G, De Dominicis G, Campione S, Accardo M, Cozzolino I, Franco R
Eur Rev Med Pharmacol Sci 2021 Jun;25(12):4236-4246. doi: 10.26355/eurrev_202106_26129. PMID: 34227091
Walpole S, Hayward NK, Pritchard AL, Johansson PA
JCO Clin Cancer Inform 2021 Jan;5:143-154. doi: 10.1200/CCI.20.00124. PMID: 33513031
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M
Nat Genet 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912. PMID: 21874000Free PMC Article

Diagnosis

Turbeville JG, Hand JL
Dermatol Clin 2023 Jan;41(1):175-185. Epub 2022 Oct 28 doi: 10.1016/j.det.2022.07.013. PMID: 36410977
Pagliuca F, Zito Marino F, Morgillo F, Della Corte C, Santini M, Vicidomini G, Guggino G, De Dominicis G, Campione S, Accardo M, Cozzolino I, Franco R
Eur Rev Med Pharmacol Sci 2021 Jun;25(12):4236-4246. doi: 10.26355/eurrev_202106_26129. PMID: 34227091
Walpole S, Hayward NK, Pritchard AL, Johansson PA
JCO Clin Cancer Inform 2021 Jan;5:143-154. doi: 10.1200/CCI.20.00124. PMID: 33513031
Cabaret O, Perron E, Bressac-de Paillerets B, Soufir N, de la Fouchardière A
Genes Chromosomes Cancer 2017 Sep;56(9):691-694. Epub 2017 Jun 23 doi: 10.1002/gcc.22473. PMID: 28560743
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M
Nat Genet 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912. PMID: 21874000Free PMC Article

Therapy

Walpole S, Hayward NK, Pritchard AL, Johansson PA
JCO Clin Cancer Inform 2021 Jan;5:143-154. doi: 10.1200/CCI.20.00124. PMID: 33513031

Prognosis

Pagliuca F, Zito Marino F, Morgillo F, Della Corte C, Santini M, Vicidomini G, Guggino G, De Dominicis G, Campione S, Accardo M, Cozzolino I, Franco R
Eur Rev Med Pharmacol Sci 2021 Jun;25(12):4236-4246. doi: 10.26355/eurrev_202106_26129. PMID: 34227091
Walpole S, Hayward NK, Pritchard AL, Johansson PA
JCO Clin Cancer Inform 2021 Jan;5:143-154. doi: 10.1200/CCI.20.00124. PMID: 33513031
Cheung M, Talarchek J, Schindeler K, Saraiva E, Penney LS, Ludman M, Testa JR
Cancer Genet 2013 May;206(5):206-10. doi: 10.1016/j.cancergen.2013.05.018. PMID: 23849051

Clinical prediction guides

Walpole S, Hayward NK, Pritchard AL, Johansson PA
JCO Clin Cancer Inform 2021 Jan;5:143-154. doi: 10.1200/CCI.20.00124. PMID: 33513031
Cheung M, Talarchek J, Schindeler K, Saraiva E, Penney LS, Ludman M, Testa JR
Cancer Genet 2013 May;206(5):206-10. doi: 10.1016/j.cancergen.2013.05.018. PMID: 23849051
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M
Nat Genet 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912. PMID: 21874000Free PMC Article

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