Methods for diagnosing a predisposition to develop cancer
Systems, methods, and computer readable media for diagnosing or characterizing a genetic predisposition to develop cancer are provided. Nucleic acids comprising a germline nucleic acid sequence encoding the BRCA1 associated protein 1 are sequenced or probed to determine if the nucleic acid sequence includes alterations that predispose a subject to develop cancer.
1. A method for delaying the onset of malignant mesothelioma in a human subject experiencing exposure to mineral fibers, wherein the human subject has a germline alteration in the BAP1gene, comprising:
obtaining a germline nucleic encoding the BAP1 protein from cells in the subject, and if the nucleic acid comprises an mRNA, optionally converting the mRNA to a cDNA,
detecting in the nucleic acid the presence of one or more germline alterations that encodes a truncated BAP1 protein biologic activity or no biologic activity, or that results in nonsense—mediated decay of BAP1 protein-encoding mRNA, and that is associated with development of malignant mesothelioma, and
treating the subject having the one or more germline alterations by reducing the amount of mineral fibers the subject is exposed to
wherein the germline alterations is a C to T-nonsense mutation in exon 16 at a position corresponding to position 52,436,624; or an A to G mutation at the splice site in intron 6 at a position corresponding to position 52,441,334.
2. The method of claim 1 , wherein the germline nucleic acid encoding the BAP1 protein comprises genomic DNA.
3. The method of claim 1 , wherein the method comprises obtaining an mRNA encoding the BAP1 protein from cells in the subject, converting the mRNA to a cDNA, and determining whether the cDNA comprises one or more germline alterations that encodes a truncated BAP1 protein having impaired biologic activity or no biologic activity and that is associated with development of malignant mesothelioma in human beings.
4. The method of claim 1 , wherein the treatment comprises reducing exposure of the subject to mineral fibers in the environment.
5. The method of claim 4 , wherein the mineral fibers comprise asbestos or erionite.
6. The method of claim 1 , wherein the determining step comprises sequencing the germline nucleic acid.
7. The method of claim 1 , wherein the determining step comprises contacting the germline nucleic acid with a detectably-labeled nucleic acid probe having a sequence that is complementary to one or more germline alterations the encodes a trunctated BAP1protein having impaired biologic activity or no biologic activity and that is associated with the development of malignant mesothelioma in human beings.
8. The method of claim 1 , wherein the alteration occurs at or proximal to an exon-intron splice site.