Liang Chung Tay

Supplementary Figure 2 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

Schematic representation of the SNVs and/or chromosomal aberrations identified in BAP1, NF2, TP53, MYH9, RHOA, MYH6, MYH10, PIK3C2A, TNFRSF1A, and 22q and 9p in a panel of 147 MPM tumors.

10.1158/0008-5472.22409303

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Supplementary Table 1 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

Whole genome sequencing data analysis of 10 MPM tumor and matched DNA generated by Complete Genomics platform

Table (database)

10.1158/0008-5472.22409300

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Supplementary Figure 1 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

Expression levels of candidate genes in 151 patients by gender and histology

Histology

Candidate gene

10.1158/0008-5472.22409306

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Supplementary Table 2 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

List of the tumor specific mutations identified by whole-genome sequencing and validated in the 10 pairs of MPM tumor and germline DNA samples

10.1158/0008-5472.22409297.v1

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Data from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

<div>AbstractMalignant 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.</div>

BAP1

Histology

10.1158/0008-5472.c.6507746

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Data from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

<div>AbstractMalignant 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.</div>

BAP1

Histology

10.1158/0008-5472.c.6507746.v1

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Supplementary Table 6 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

List of the Tumor types having mutations in both MYH9 and RHOA genes in the cBioPortal for Cancer Genomics database

Table (database)

10.1158/0008-5472.22409285.v1

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Supplementary Table 4 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

List of the 51 canonical pathways significantly enriched (p<0.05) for the mutated genes identify by Ingenuity Pathway Analysis

Ingenuity

Pathway Analysis

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10.1158/0008-5472.22409291.v1

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Supplementary Table 5 from Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

List of SNVs identified in the analyzed genes

Table (database)

10.1158/0008-5472.22409288

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Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

Cancer Research (2015)

Assunta De Rienzo Michael A. Archer Beow Y. Yeap Nhien Dao Daniele Sciaranghella

Abstract 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.

10.1158/0008-5472.can-15-0751

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Liang Chung Tay

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