Dataset Information

Global expression analysis of BAP1 knockdown in transfected 92.1 cells

ABSTRACT: Analysis of the effect that reduced BAP1 levels have on global gene expression.The hypothesis tested was that reduction in BAP1 levels would produce changes in gene expression similar to changes observed in class 2 uveal melanomas. Data provided insight into genes that are disrupted with reduced BAP1 levels. Total RNA was isolated from 92.1 cells transfected with either control or BAP1 knockdown constructs for global expression analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Shenghui Duan Katie A Matatall Michael D Onken Elisha D.O. Roberson M L Council Elisha D Roberson Lori A Worley J W Harbour Anne M Bowcock Li Cao Cynthia Helms

PROVIDER: E-GEOD-24896 | ArrayExpress | 2011-01-06

SECONDARY ACCESSION(S): GSE24896PRJNA132077

REPOSITORIES: GEO, ArrayExpress

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Publications

Frequent mutation of BAP1 in metastasizing uveal melanomas.

Harbour J William JW Onken Michael D MD Roberson Elisha D O ED Duan Shenghui S Cao Li L Worley Lori A LA Council M Laurin ML Matatall Katie A KA Helms Cynthia C Bowcock Anne M AM

Science (New York, N.Y.) 20101104 6009

Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutati ...[more]

PMID: 21051595

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Project description:We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 91 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). Overall design: Mesothelioma patients with family histories including multiple mesotheliomas and melanomas and/or multiple cancers were screened for mutations in BAP1. Four apparently un-related individuals were identified that carried an identical truncating mutation in BAP1 that was not present in any examined genetic database. To identify whether the mutation was inherited-by-descent from a common ancestor, the four subjects and four normal donors were genotyped using genome-wide Ilumina micro-arrays from which principal component, identity-by-descent, and shared haplotype analyses were performed.