BAP1 Tumor Predisposition Syndrome

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1		Catherine Yang	+ 822 word(s)	822	2020-12-15 07:17:04

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/bap1-tumor-predisposition-syndrome

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.

genetic conditions

1. Introduction

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.

2. Frequency

BAP1 tumor predisposition syndrome is a rare condition; its prevalence is unknown. More than 70 families with the condition have been described in the medical literature.

3. Causes

BAP1 tumor predisposition syndrome is caused by mutations in the BAP1 gene. The BAP1 protein acts as a tumor suppressor, which means it helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. Its function is to remove molecules called ubiquitin from certain proteins (deubiquitination), which can affect the activity of the protein and its interactions with other proteins. By removing ubiquitin, BAP1 helps regulate diverse cellular processes. The BAP1 protein is thought to be involved in cell growth and division (proliferation), cell death, repair of damaged DNA, and control of gene activity.

Mutations in the BAP1 gene lead to production of an altered protein that cannot function normally and may be broken down prematurely. In addition to an inherited (germline) mutation in one copy of the gene, which is found in essentially every cell of the body, a second, non-inherited (somatic) mutation usually occurs in the normal copy of the gene in cells that give rise to tumors. Together, the germline and somatic mutations result in a complete loss of BAP1 protein function in tumor cells. A shortage of this protein's function likely impairs the removal of ubiquitin from certain proteins. Although it is unclear exactly how loss of BAP1 function leads to BAP1 tumor predisposition syndrome, researchers speculate that altered activity of proteins normally regulated by BAP1 deubiquitination may promote cell proliferation or survival, resulting in tumor formation.

Studies suggest that environmental and lifestyle factors help determine which types of tumor develop in individuals with BAP1 tumor predisposition syndrome. For example, exposure to asbestos likely contributes to the development of malignant mesothelioma. While asbestos increases the risk of malignant mesothelioma in the general population, the risk is even higher in individuals with a BAP1 gene mutation. It is not clear why certain tumor types are particularly associated with BAP1 tumor predisposition syndrome.

4. Inheritance

BAP1 tumor predisposition syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered BAP1 gene increases the chance of developing one or more tumors. In most cases, an affected person has one parent with the condition.

People with a mutation in the BAP1 gene inherit an increased risk of tumor formation. Not all people with a gene mutation will develop a tumor.

5. Other Names for This Condition

BAP1-related tumor predisposition syndrome
BAP1-TPDS
COMMON syndrome
cutaneous/ocular melanoma, atypical melanocytic proliferations, and other internal neoplasms

References

Baumann F, Flores E, Napolitano A, Kanodia S, Taioli E, Pass H, Yang H,Carbone M. Mesothelioma patients with germline BAP1 mutations have 7-foldimproved long-term survival. Carcinogenesis. 2015 Jan;36(1):76-81. doi:10.1093/carcin/bgu227.
Cheung M, Kadariya Y, Talarchek J, Pei J, Ohar JA, Kayaleh OR, Testa JR.Germline BAP1 mutation in a family with high incidence of multiple primarycancers and a potential gene-environment interaction. Cancer Lett. 2015 Dec28;369(2):261-5. doi: 10.1016/j.canlet.2015.09.011.
Mochel MC, Piris A, Nose V, Hoang MP. Loss of BAP1 Expression in Basal CellCarcinomas in Patients With Germline BAP1 Mutations. Am J Clin Pathol. 2015Jun;143(6):901-4. doi: 10.1309/AJCPG8LFJC0DHDQT.
Ohar JA, Cheung M, Talarchek J, Howard SE, Howard TD, Hesdorffer M, Peng H,Rauscher FJ, Testa JR. Germline BAP1 Mutational Landscape of Asbestos-ExposedMalignant Mesothelioma Patients with Family History of Cancer. Cancer Res. 2016Jan 15;76(2):206-15. doi: 10.1158/0008-5472.CAN-15-0295.Erratum in: Cancer Res. 2017 Jun 1;77(11):3124. Cancer Res. 2018 Jan 1;78(1):309.
Pilarski R, Carlo M, Cebulla C, Abdel-Rahman M. BAP1 Tumor PredispositionSyndrome. 2016 Oct 13 [updated 2020 Sep 17]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet].Seattle (WA): University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK390611/
Popova T, Hebert L, Jacquemin V, Gad S, Caux-Moncoutier V, Dubois-d'Enghien C,Richaudeau B, Renaudin X, Sellers J, Nicolas A, Sastre-Garau X, Desjardins L,Gyapay G, Raynal V, Sinilnikova OM, Andrieu N, Manié E, de Pauw A, Gesta P,Bonadona V, Maugard CM, Penet C, Avril MF, Barillot E, Cabaret O, Delattre O,Richard S, Caron O, Benfodda M, Hu HH, Soufir N, Bressac-de Paillerets B,Stoppa-Lyonnet D, Stern MH. Germline BAP1 mutations predispose to renal cellcarcinomas. Am J Hum Genet. 2013 Jun 6;92(6):974-80. doi:10.1016/j.ajhg.2013.04.012.
Rai K, Pilarski R, Boru G, Rehman M, Saqr AH, Massengill JB, Singh A, MarinoMJ, Davidorf FH, Cebulla CM, H Abdel-Rahman M. Germline BAP1 alterations infamilial uveal melanoma. Genes Chromosomes Cancer. 2017 Feb;56(2):168-174. doi:10.1002/gcc.22424.
Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH. Comprehensive review of BAP1tumor predisposition syndrome with report of two new cases. Clin Genet. 2016Mar;89(3):285-94. doi: 10.1111/cge.12630.
Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, Windpassinger C,Wackernagel W, Loy S, Wolf I, Viale A, Lash AE, Pirun M, Socci ND, Rütten A,Palmedo G, Abramson D, Offit K, Ott A, Becker JC, Cerroni L, Kutzner H, BastianBC, Speicher MR. Germline mutations in BAP1 predispose to melanocytic tumors. NatGenet. 2011 Aug 28;43(10):1018-21. doi: 10.1038/ng.910.

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Subjects: Genetics & Heredity

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Catherine Yang

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Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The gene associated with BAP1 tumor predisposition syndrome

4. Inheritance

5. Other Names for This Condition

References