Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma
| Autor: | Yaoyu E. Wang, Yifan Zheng, Michael A. Archer, John Quackenbush, William G. Richards, Lucian R. Chirieac, Soo Meng Ching, Stephen Rudd, Renee Rubio, Daniele Sciaranghella, Antonios C. Sideris, Paola Dal Cin, Kiara J. Munir, Beow Y. Yeap, Nhien Dao, Robert Hercus, Raphael Bueno, Corinne E. Gustafson, Liang Chung Tay, David J. Sugarbaker, Alexander G. Holman, Larry Croft, Jesse R. Battilana, James R. Wong, Jonathan A. Fletcher, Assunta De Rienzo, Peter E. Sugarbaker |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology Adult Male Mesothelioma Cancer Research Pathology medicine.medical_specialty RHOA Lung Neoplasms Adolescent Pleural Neoplasms Article 03 medical and health sciences Young Adult 0302 clinical medicine Sex Factors CDKN2A Internal medicine Biomarkers Tumor Medicine Humans Pleural Neoplasm Young adult Aged Aged 80 and over BAP1 biology business.industry Mesothelioma Malignant Case-control study Middle Aged medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Case-Control Studies Cohort biology.protein Female business |
| Zdroj: | Cancer research. 76(2) |
| ISSN: | 1538-7445 |
| Popis: | Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. Cancer Res; 76(2); 319–28. ©2015 AACR. |
| Databáze: | OpenAIRE |
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