In Arrayed Ranks: Array Technology in the Study of Mesothelioma

Gray, Steven G.; Fennell, Dean A.; Mutti, Luciano; O’Byrne, Kenneth J.

doi:10.1097/jto.0b013e3181951ce8

Cited by 15 publications

(14 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Seven chromosomal regions were significantly associated with MPM in the region-based analysis ( P <0.0025, Table 3, Figure 2, Figure S3) [20]. The gene-based analysis confirmed the significance of the THRB gene ( P = 2.29×10 −5 ) and showed a borderline significance for the PVT1 gene ( P = 0.02) (Table 3).…”

Section: Resultsmentioning

confidence: 62%

“…Although no link with MPM has been previously reported for SLC7A14 , a chromosomal gain has been described in this region [20], suggesting a possible involvement of other genes in MPM.…”

Section: Discussionmentioning

confidence: 61%

“…None of the 12 genotyped SNPs with the highest significance levels in the Italian study were found in the Australian replication study (Table S4), and nor of these were confirmed by the meta-analysis (Table S5). Nevertheless, when a regional analysis was performed in the Australian study sample, we found significant associations in five chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14) that have reported to be altered in mesothelioma (Table 5) [20].…”

Section: Resultsmentioning

confidence: 84%

“…Among the top SNPs identified in our Italian study sample, there were several genes previously reported to be involved in MPM or other cancer types, as well as chromosomal regions reported to be altered in MPM [20].…”

Section: Discussionmentioning

confidence: 95%

See 3 more Smart Citations

Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

et al. 2013

View full text Add to dashboard Cite

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors.To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia.Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14).Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28).These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

show abstract

Section: Resultsmentioning

confidence: 62%

“…Although no link with MPM has been previously reported for SLC7A14 , a chromosomal gain has been described in this region [20], suggesting a possible involvement of other genes in MPM.…”

Section: Discussionmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 95%

See 2 more Smart Citations

Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

et al. 2013

View full text Add to dashboard Cite

show abstract

“…INK4a / p14 ARF and NF2 (neurofibromatosis type 2) tumor suppressor genes (TSG) and recent comprehensive analyses have identified other candidate cancer-associated genes responsible for MM development, progression, and poor outcome (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

LATS2 Is a Tumor Suppressor Gene of Malignant Mesothelioma

et al. 2011

View full text Add to dashboard Cite

Malignant mesothelioma (MM) is an aggressive neoplasm associated with asbestos exposure. We carried out genome-wide array-based comparative genomic hybridization analysis with 14 MM cell lines. Three cell lines showed overlapping homozygous deletion at chromosome 13q12, which harbored the LATS2 (large tumor suppressor homolog 2) gene. With 6 other MM cell lines and 25 MM tumors, we found 10 inactivating homozygous deletions or mutations of LATS2 among 45 MMs. LATS2 encodes a serine/threonine kinase, a component of the Hippo tumor-suppressive signaling pathway, and we transduced LATS2 in MM cells with its mutation. Transduction of LATS2 inactivated oncoprotein YAP, a transcriptional coactivator, via phosphorylation, and inhibited MM cell growth. We also analyzed LATS2 immunohistochemically and found that 13 of 45 MM tumors had low expression of LATS2. Because NF2 is genetically mutated in 40% to 50% of MM, our data indicate that Hippo pathway dysregulation is frequent in MM cells with inactivation of LATS2 or an upstream regulator of this pathway, Merlin, which is encoded by NF2. Thus, our results suggest that the inactivation of LATS2 is one of the key mechanisms for constitutive activation of YAP, which induces deregulation of MM cell proliferation.

show abstract

Malignant Mesothelioma

Dobra

Hjerpe

2011

Serous Effusions

View full text Add to dashboard Cite

In Arrayed Ranks: Array Technology in the Study of Mesothelioma

Cited by 15 publications

References 149 publications

Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

LATS2 Is a Tumor Suppressor Gene of Malignant Mesothelioma

Malignant Mesothelioma

Contact Info

Product

Resources

About