Cancer Genetics

Our medical research library holds 9 studies published in Cancer Genetics (2012–2021). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 9 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier
• Published: 2011 to the present, United States
• Language: English
• ISSN: 2210-7762 (print)
• Continues: Cancer Genetics and Cytogenetics
• Its record in the NLM Catalog

2020s

• The spectrum of tumors harboring BAP1 gene alterations. Y. Laitman, J. Newberg, R.B. Molho, et al. 2021;256-257:31-35. PubMed · Publisher

  Abstract

  Germline mutations in the BRCA1-associated protein (BAP1) gene (MIM # 603089) are associated with a substantially increased risk for developing melanoma, mesothelioma, and renal cell carcinoma. Somatic inactivation of the BAP1 gene was noted in these and other tumors types, including esophageal cancer and cholangiocarcinoma. The favorable response of BRCA1/2-associated tumors to poly (ADP-ribose) polymerase (PARP) inhibitor therapy, raises the possibility that tumors harboring BAP1 mutations may exhibit similar sensitivity to PARP inhibitor therapy. Given the possibility that BAP1 alterations may have therapeutic implications, this study was aimed to describe the spectrum of tumors that harbor BAP1 alterations. The Foundation Medicine database was queried for known or likely pathogenic BAP1 genomic variants through July 2019. Overall, 4982/374,694 (1.81%) tumors harbored pathogenic BAP1 genomic alterations. Highest rates were noted in mesothelioma (45.24%), cholangiocarcinoma (13.37%), renal cell carcinoma (10.52%), thymic cancer (8.16%), salivary gland cancer (6.18%), and melanoma (5.1%). There were 59 unique BAP1 short variants detected in at least 10 samples. More same tissue tumors of squamous cell histology harbored BAP1 alterations than adenocarcinomas. The current study highlights tumor types that display higher than previously appreciated rates of somatic BAP1 genomic alterations.

  Copyright © 2021. Published by Elsevier Inc.

• Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos. G. Brandi, M. Deserti, A. Palloni, et al. 2020;248-249:57-62. Case report PubMed · Publisher

  Abstract

  BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.

  Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

2010s

• BAP1 gene mutations in Egyptian patients with advanced sporadic malignant pleural mesothelioma (MPM): relation with clinical outcomes and survival. A.A. Bahnasy, R.S. El-Din, N.A. Sabri, et al. 2018;228-229:83-92. PubMed · Publisher

  Abstract

  Background: Malignant Pleural Mesothelioma (MPM) is a lethal cancer with few therapeutic options. Patients with MPM have a poor prognosis, with estimated 1 year median survival and currently no treatment is curative. The BRCA associated protein 1 (BAP1) has the highest prevalence of protein-altering mutations identified in MPM.

  Aims: Assessment of the frequency and pattern of BAP1 gene mutations in Egyptian patients with advanced sporadic MPM in relation to disease progression and survival rates in order to identify a novel therapeutic target for MPM.

  Methods: This prospective, cohort study included 122 patients who were diagnosed and treated as advanced MPM. BAP1 gene mutations were assessed from circulating tumor cells (CTCs) by polymerase chain reaction (PCR) and sequencing and these mutations have been confirmed using the tumor tissue. BAP1 immunohistochemistry was performed using the Dako Envision visualization system. The relationship between BAP1 gene mutations, PFS and OS rates was assessed using the log rank test. The relationship between BAP1 gene mutations, clinical response and patient's clinicopathological characteristics was assessed using chi-square test.

  Results: Forty seven (38.5%) MPM cases showed one or more mutations in BAP1 gene. The presence of BAP1 mutations associated significantly with BAP1 protein expression (p < 0.001), the incidence of organ metastasis (p = 0.04), PFS after second line treatment (p = 0.04) and clinical response after second line treatment (p = 0.01) only.

  Conclusion: BAP1 gene mutations are relatively common in Egyptian patients with advanced sporadic MPM. BAP1 mutations are associated with disease progression especially after second line therapy and the incidence of organ metastasis.

  Copyright © 2018 Elsevier Inc. All rights reserved.

• A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer. K.J. McDonnell, G.T. Gallanis, K.A. Heller, et al. 2016;209(3):75-81. PubMed · Publisher · Free full text

  Abstract

  Germline mutations in the tumor suppressor gene, BRCA-1 associated protein (BAP1), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 c.1777C>T germline mutation developed other neoplastic disease including thyroid cancer. IHC analysis of the thyroid cancer, as well, demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further highlights the relevance of BAP1 as a clinically important tumor suppressor gene, and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1-associated neoplastic disease.

  Copyright © 2015 Elsevier Inc. All rights reserved.

• Mesothelioma families without inheritance of a BAP1 predisposing mutation. V. Ascoli, I. Cozzi, S. Vatrano, et al. 2016;209(9):381-387. PubMed · Publisher

  Abstract

  Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic). On the other hand, we identified a novel BAP1 somatic alteration (c.329_335delinsTC) in exon 5 (n = 1 biphasic), and we hypothesized the occurrence of somatic inactivating events not identifiable by sequencing in the other cases (n = 3 epithelioid), as demonstrated by the loss of nuclear BAP1 immunostaining. History of other cancers was in sites not typical of the BAP1 cancer syndrome. Asbestos exposure was occupational (n = 2 clusters), household (n = 1), and unknown (n = 1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1-unmutated families.

  Copyright © 2016 Elsevier Inc. All rights reserved.

• An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation. M. Cheung, Y. Kadariya, J. Pei, et al. 2015;208(10):502-7. PubMed · Publisher · Free full text

  Abstract

  We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family.

  Copyright © 2015 Elsevier Inc. All rights reserved.

• Further evidence for germline BAP1 mutations predisposing to melanoma and malignant mesothelioma. M. Cheung, J. Talarchek, K. Schindeler, et al. 2013;206(5):206-10. Case report · Review PubMed · Publisher

  Abstract

  We describe a new family with a novel germline BAP1 nonsense mutation, c.723T>G, which leads to a predicted truncated protein, p.Y241*, or nonsense-mediated decay of the BAP1 mRNA. The proband had uveal melanoma (UM), and his paternal family has a remarkable history of multiple cancers. The proband's father had both pleural malignant mesothelioma (MM) and cutaneous melanoma (CM); a paternal uncle had lung cancer, CM, and UM; and a grandmother had CM. The findings in this family provide further support for the existence of a BAP1 cancer syndrome that predisposes to MM, various melanocytic neoplasms, and potentially other cancers. The fact that several members of the family manifested two or more different types of cancer suggests widespread BAP1-related tumor susceptibility targeting tissues of multiple organs. In addition, a review of BAP1 cancer syndrome families reported to date indicates that the location of the BAP1 mutation does not have any bearing on the spectrum of cancer types observed, either for mesothelial or melanocytic tumors.

  Copyright © 2013 Elsevier Inc. All rights reserved.

• Integrated high-resolution array CGH and SKY analysis of homozygous deletions and other genomic alterations present in malignant mesothelioma cell lines. G. Klorin, E. Rozenblum, O. Glebov, et al. 2013;206(5):191-205. PubMed · Publisher · Free full text

  Abstract

  High-resolution oligonucleotide array comparative genomic hybridization (aCGH) and spectral karyotyping (SKY) were applied to a panel of malignant mesothelioma (MMt) cell lines. SKY has not been applied to MMt before, and complete karyotypes are reported based on the integration of SKY and aCGH results. A whole genome search for homozygous deletions (HDs) produced the largest set of recurrent and non-recurrent HDs for MMt (52 recurrent HDs in 10 genomic regions; 36 non-recurrent HDs). For the first time, LINGO2, RBFOX1/A2BP1, RPL29, DUSP7, and CCSER1/FAM190A were found to be homozygously deleted in MMt, and some of these genes could be new tumor suppressor genes for MMt. Integration of SKY and aCGH data allowed reconstruction of chromosomal rearrangements that led to the formation of HDs. Our data imply that only with acquisition of structural and/or numerical karyotypic instability can MMt cells attain a complete loss of tumor suppressor genes located in 9p21.3, which is the most frequently homozygously deleted region. Tetraploidization is a late event in the karyotypic progression of MMt cells, after HDs in the 9p21.3 region have already been acquired.

  Published by Elsevier Inc.

• Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum. H. Nemoto, G. Tate, K. Kishimoto, et al. 2012;205(11):594-8. Case report PubMed · Publisher

  Abstract

  Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associated not only with malignant pleural mesothelioma, but also with WDPMP.

  Copyright © 2012 Elsevier Inc. All rights reserved.

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