ArticleProceedings of the National Academy of Sciences of the United States of America2016
High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 150 citations in OpenAlex.
- Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma.Scientific reports · 2017Trial
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Advances in the Basic Sciences in Thoracic Oncology in the Last 20 Years and Their Translational Impact.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- The genetics of cancer heterogeneity and mesothelioma.Frontiers in oncology · 2026Review
- An overview of BAP1 biological functions and current therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Expanded detection and impact ofNAR cancer · 2024Article
- Biomarkers to predict the benefits of immune‑checkpoint blockade‑based therapy in patients with malignant peritoneal mesothelioma (Review).Oncology letters · 2024Review
- Individualized Cell-Free DNA Monitoring With Chromosomal Junctions for Mesothelioma.JTO clinical and research reports · 2024Article
- Mesothelioma Cases in the World Trade Center Survivors.Annals of case reports · 2024Article
- Comparison of Immunohistochemistry, Next-generation Sequencing and Fluorescence In Situ Hybridization for Detection of MTAP Loss in Pleural Mesothelioma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.Journal of thoracic disease · 2024Review
- Review
- Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma.Journal of translational medicine · 2023Review
- SETDB1 tumour suppressor roles in near-haploid mesothelioma involve TP53.British journal of cancer · 2023Article
- CAMK2D: a novel molecular target for BAP1-deficient malignant mesothelioma.Cell death discovery · 2023Article
- BAP1 as a guardian of genome stability: implications in human cancer.Experimental & molecular medicine · 2023Review
- BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.Oncogene · 2023Article
- BAP1 is a novel regulator of HIF-1α.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.Frontiers in immunology · 2023Article
- Myxoid pleomorphic liposarcoma is distinguished from other liposarcomas by widespread loss of heterozygosity and significantly worse overall survival: a genomic and clinicopathologic study.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
We used a custom-made comparative genomic hybridization array (aCGH; average probe interval 254 bp) to screen 33 malignant mesothelioma (MM) biopsies for somatic copy number loss throughout the 3p21 region (10.7 Mb) that harbors 251 genes, including BRCA1 (breast cancer 1)-associated protein 1 (BAP1), the most commonly mutated gene in MM. We identified frequent minute biallelic deletions (<3 kb) in 46 of 251 genes: four were cancer-associated genes: SETD2 (SET domain-containing protein 2) (7 of 33), BAP1 (8 of 33), PBRM1 (polybromo 1) (3 of 33), and SMARCC1 (switch/sucrose nonfermentable- SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily c, member 1) (2 of 33). These four genes were further investigated by targeted next-generation sequencing (tNGS), which revealed sequence-level mutations causing biallelic inactivation. Combined high-density aCGH and tNGS revealed biallelic gene inactivation in SETD2 (9 of 33, 27%), BAP1 (16 of 33, 48%), PBRM1 (5 of 33, 15%), and SMARCC1 (2 of 33, 6%). The incidence of genetic alterations detected is much higher than reported in the literature because minute deletions are not detected by NGS or commercial aCGH. Many of these minute deletions were not contiguous, but rather alternated with segments showing oscillating copy number changes along the 3p21 region. In summary, we found that in MM: (i) multiple minute simultaneous biallelic deletions are frequent in chromosome 3p21, where they occur as distinct events involving multiple genes; (ii) in addition to BAP1, mutations of SETD2, PBRM1, and SMARCC1 are frequent in MM; and (iii) our results suggest that high-density aCGH combined with tNGS provides a more precise estimate of the frequency and types of genes inactivated in human cancer than approaches based exclusively on NGS strategy.
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