Cell Death and Differentiation, June 30, 2017 (doi: 10.1038/cdd.2017.95)
Aerobic glycolysis, also known as the ‘Warburg effect’, does not necessarily occur as an adaptive process that is consequence of carcinogenesis, but rather that it may also predate malignancy by many years and facilitate carcinogenesis.
Nature International Weekly Journal of Science (2017) - doi:10.1038/nature22798
A mechanistic rationale for the ability of BAP1 to regulate gene-environment interaction in human carcinogenesis
A Review of our Projects, Publications, and Discoveries
High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma
We found that gene mutations/deletions are frequent in mesothelioma and occur through a variety of DNA alterations. We identified genes implicated in malignant mesothelioma: SETD2, SMARCC1, PBRM1.
Differentiating between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in malignant mesothelioma and less frequently positive in carcinomas, and vice versa. However, in 10 to 20% of the cases, the immunohistochemical staining results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy.
We stained 45 non-small cell lung cancers (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include calretinin, Wilms Tumor 1, cytokeratin 5, podoplantin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM. Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 staining helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.
Authors: Michele Carbone, David Shimizu, Andrea Napolitano, Mika Tanji, Harvey I. Pass, Haining Yang, Sandra Pastorino