High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma

Nasu, Masaki; Emi, Mitsuru; Pastorino, Sandra; Tanji, Mika; Powers, Amy; Luk, Hugh; Baumann, Francine; Zhang, Yu-an; Gazdar, Adi; Kanodia, Shreya; Tiirikainen, Maarit; Flores, Erin; Gaudino, Giovanni; Becich, Michael J.; Pass, Harvey I.; Yang, Haining; Carbone, Michele

doi:10.1097/JTO.0000000000000471

Back to Previous Page

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma

Published Date:

Apr 2015

Publisher's site:

http://dx.doi.org/10.1097/JTO.0000000000000471 New Site Icon

Source:

J Thorac Oncol. 10(4):565-576.

[PDF-1.50 MB]

Details:

Personal Authors:

Nasu, Masaki ; Emi, Mitsuru ; Pastorino, Sandra ; Tanji, Mika ; Powers, Amy ; ... More ▼

Keywords:

[+]

Pubmed ID:

25658628

Pubmed Central ID:

PMC4408084

Description:

Background

BAP1 is a nuclear deubiquitinase that regulates gene expression, transcription, DNA repair, and more. Several findings underscore the apparent “driver” role of BAP1 in malignant mesothelioma (MM). However the reported frequency of somatic BAP1 mutations in MM varies considerably, a discrepancy that appeared related to either methodological or ethnical differences across various studies.

Methods

To address this discrepancy, we carried out comprehensive genomic and immunohistochemical (IHC) analyses to detect somatic BAP1 gene alterations in 22 frozen MM biopsies from US MM patients.

Results

By combining Sanger sequencing, Multiplex Ligation-Dependent Probe Amplification, copy number analysis and cDNA sequencing, we found alteration of BAP1 in 14/22 biopsies (63.6%). No changes in methylation were observed. IHC revealed normal nuclear BAP1 staining in the 8 MM containing wild-type BAP1, while no nuclear staining was detected in the 14 MM biopsies containing tumor cells with mutated BAP1. Thus, IHC results were in agreement with those obtained by genomic analyses. We then extended IHC analysis to an independent cohort of 70 MM biopsies, of which there was insufficient material to perform molecular studies. IHC revealed loss of BAP1 nuclear staining in 47 out of these 70 MM biopsies (67.1%).

Conclusions

Our findings conclusively establish BAP1 as the most commonly mutated gene in MM, regardless of ethnic background or other clinical characteristics. Our data point to IHC as the most accessible and reliable technique to detect BAP1 status in MM biopsies.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

2U24-OH009077-08/OH/NIOSH CDC HHS/United States
P01 CA114047/CA/NCI NIH HHS/United States
P01CA114047/CA/NCI NIH HHS/United States
P30 CA071789/CA/NCI NIH HHS/United States
P30CA071789/CA/NCI NIH HHS/United States
R01 CA160715/CA/NCI NIH HHS/United States
R01CA106567/CA/NCI NIH HHS/United States
R01CA160715-0A/CA/NCI NIH HHS/United States

Main Document Checksum:

[+]

Supporting Files:

	NIHMS653565-supplement-Supplemental_Digital_Content_7.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_8.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	NIHMS653565-supplement-Supplemental_Digital_Content_9.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	nihms653565.nxml	application/octet-stream
	nihms653565f1.gif	image/gif
	nihms653565f1.jpg	image/jpeg
	nihms653565f2.gif	image/gif
	nihms653565f2.jpg	image/jpeg
	nihms653565f3.gif	image/gif
	nihms653565f3.jpg	image/jpeg
	NIHMS653565-supplement-Supplemental_Digital_Content_1.docx	application/vnd.openxmlformats-officedocument.wordprocessingml.document
	nihms653565f4.gif	image/gif
	nihms653565f4.jpg	image/jpeg
	nihms653565f5.gif	image/gif
	nihms653565f5.jpg	image/jpeg
	NIHMS653565-supplement-Supplemental_Digital_Content_10.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_11.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_2.docx	application/vnd.openxmlformats-officedocument.wordprocessingml.document
	NIHMS653565-supplement-Supplemental_Digital_Content_3.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_4.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_5.tif	image/tiff
	NIHMS653565-supplement-Supplemental_Digital_Content_6.tif	image/tiff

No Related Documents.

You May Also Like:

Meeting Report: Mode(s) of Action of Asbestos and Related Mineral Fibers

Personal Author:

Gwinn, Maureen R.; DeVoney, Danielle; Jarabek, Annie M.; Sonawane, Babasaheb; Wheeler, John; Weissman, David N.; Masten, Scott; Thompson, Claudia;

Published:

Aug 01 2011

Source:

Environ Health Perspect. 2011; 119(12):1806-1810.

Description:

Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and re...

File Type:

[PDF - 161.38 KB]
CD30 is a potential therapeutic target in malignant mesothelioma

Personal Author:

Dabir, Snehal; Kresak, Adam; Yang, Michael; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin;

Published:

Jan 14 2015

Source:

Mol Cancer Ther. 14(3):740-746.

Description:

CD30 is a cytokine receptor belonging to the TNF superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin disease and anaplastic large cell lymphoma. There have been sporadic r...

File Type:

[PDF - 761.47 KB]
Raw Single-Wall Carbon Nanotubes Induce Oxidative Stress and Activate MAPKs, AP-1, NF-κB, and Akt in Normal and Malignant Human Mesothelial Cells

Personal Author:

Pacurari, Maricica; Yin, Xuejun J.; Zhao, Jinshun; Ding, Ming; Leonard, Steve S.; Schwegler-Berry, Diane; Ducatman, Barbara S.; Sbarra, Deborah; Hoover, Mark D.; Castranova, Vincent; Vallyathan, Val;

Published:

Sep 2008

Source:

Environ Health Perspect. 2008; 116(9):1211-1217.

Description:

Background : Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of t...

File Type:

[PDF - 251.82 KB]
Epidemiologic and Molecular Prognostic Review of Glioblastoma

Personal Author:

Thakkar, Jigisha P.; Dolecek, Therese A.; Horbinski, Craig; Ostrom, Quinn T.; Lightner, Donita D.; Barnholtz-Sloan, Jill S.; Villano, John L.;

Published:

Jul 22 2014

Source:

Cancer Epidemiol Biomarkers Prev. 23(10):1985-1996.

Description:

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. ...

File Type:

[PDF - 1.70 MB]
Toxicological profile for asbestos

Personal Author:

Hanley, G. Douglas

Corporate Author:

Syracuse Research Corporation. United States. Agency for Toxic Substances and Disease Registry..

Published:

September 2001

Series:

TP (Series) (Atlanta, Ga.)

Description:

Public health statement -- Relevance to public health -- Health effects -- Chemical and physical information -- Production, import/export, use, and disposal -- Potential for human exposure -- Analytical methods -- Regulations and advisories.

File Type:

[PDF - 3.97 MB]