Mesothelioma Molecular and Genetic Testing - Revision history

MesotheliomaSupport: Add differentiated triple GEO format: At-a-Glance, Key Facts wikitable, FAQ, Quick Statistics, Get Help

2026-03-08T22:37:30Z

Add differentiated triple GEO format: At-a-Glance, Key Facts wikitable, FAQ, Quick Statistics, Get Help

MesotheliomaSupport: Remove H1, convert exec summary to lead, add listicle

2026-02-24T06:41:16Z

Remove H1, convert exec summary to lead, add listicle

← Older revision		Revision as of 06:41, 24 February 2026
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	! colspan="2" style="background:#1a5276; color:white; padding:12px; font-size:1.1em; text-align:center;" \| Molecular & Genetic Testing		! colspan="2" style="background:#1a5276; color:white; padding:12px; font-size:1.1em; text-align:center;" \| Molecular & Genetic Testing
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	\| colspan="2" style="padding:10px; text-align:center; font-style:italic; border-bottom:1px solid #dee2e6;" \| Genomic Profiling for [[Mesothelioma]]		\| colspan="2" style="padding:10px; text-align:center; font-style:italic; border-bottom:1px solid #dee2e6;" \| Genomic Profiling for Mesothelioma
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	~~= Mesothelioma~~ Molecular and ~~Genetic Testing: How~~ BAP1, CDKN2A, and ~~NGS Panels Guide Diagnosis~~ and ~~Treatment~~ =		'''Molecular and genetic testing''' has fundamentally transformed the diagnosis and management of '''malignant mesothelioma''', moving the field beyond traditional histologic classification toward '''precision oncology''' approaches that match patients with targeted therapies and clinical trials. The three most clinically significant molecular alterations in mesothelioma are '''BAP1 loss''' (found in approximately 60% of pleural mesotheliomas), '''CDKN2A homozygous deletion''' (45–74% of pleural cases), and '''NF2 inactivation''' (30–40%), each providing both diagnostic and prognostic information that directly impacts patient care.<ref name="pmc_bap1_pleural" /><ref name="nature_cdkn2a" /><ref name="pmc_nf2_alteration" />

	== ~~Executive Summary =~~=		BAP1 immunohistochemistry and CDKN2A fluorescence in situ hybridization represent the two most important ancillary tests for distinguishing malignant mesothelioma from reactive mesothelial proliferations, a diagnostic challenge that has historically delayed treatment. BAP1 IHC achieves '''53% sensitivity with 86% specificity''', while CDKN2A FISH achieves '''41–61% sensitivity with 100% specificity''' — meaning a positive CDKN2A FISH result definitively confirms malignancy. When combined, these tests significantly improve diagnostic accuracy beyond either test alone.<ref name="pubmed_bap1_cdkn2a" /><ref name="pubmed_cdkn2a_cish" /><ref name="dandell_diagnosis" />

	~~Molecular~~ and ~~genetic testing has fundamentally transformed the diagnosis and management~~ of ~~malignant mesothelioma~~, ~~moving the field beyond traditional histologic classification toward precision oncology approaches that match patients with~~ targeted ~~therapies and [[Clinical Trials\|clinical trials]]~~. ~~The three most clinically significant molecular alterations in~~ mesothelioma ~~are~~ BAP1 ~~loss (found in approximately 60%~~ of ~~pleural mesotheliomas)~~, ~~CDKN2A homozygous deletion (45–74~~% of ~~pleural cases)~~, ~~and NF2 inactivation (30–40%)~~, ~~each providing both diagnostic~~ and ~~prognostic information that directly impacts patient care~~.<ref name="~~pmc_bap1_pleural~~" /><ref name="~~nature_cdkn2a~~" /><ref name="~~pmc_nf2_alteration~~" />		Next-generation sequencing panels such as '''FoundationOne CDx (324 genes)''' and '''MSK-IMPACT (341 genes)''' enable comprehensive genomic profiling that identifies rare actionable mutations in 1–2% of cases, including ALK rearrangements responsive to targeted therapy. For the '''9–12% of mesothelioma patients''' carrying germline BAP1 mutations, genetic testing triggers cascade screening of family members and lifelong cancer surveillance, as these mutations confer a '''30% lifetime risk''' of mesothelioma along with elevated risks of uveal melanoma, renal cell carcinoma, and other cancers.<ref name="pmc_ngs_clinical" /><ref name="pmc_genetic_susceptibility" /><ref name="mlc_diagnosis" />

	~~BAP1 immunohistochemistry~~ and ~~CDKN2A fluorescence in situ hybridization represent the two most important ancillary tests for distinguishing malignant mesothelioma from reactive mesothelial proliferations,~~ a ~~diagnostic challenge that has historically delayed treatment.~~ BAP1 ~~IHC achieves 53~~% ~~sensitivity with 86~~% ~~specificity, while~~ CDKN2A FISH achieves ~~41–61% sensitivity with~~ 100% specificity ~~— meaning a positive CDKN2A FISH result definitively confirms malignancy. When combined, these tests significantly improve diagnostic accuracy beyond either test alone.~~<ref name="pubmed_bap1_cdkn2a" /><ref name="~~pubmed_cdkn2a_cish~~" /><ref name="~~dandell_diagnosis~~" />		'''Mesothelioma molecular and genetic testing at a glance:'''
			* '''BAP1 loss prevalence''' — detected in approximately 60% of pleural mesotheliomas and up to 80% of epithelioid subtype tumors<ref name="pmc_bap1_pleural" />
	~~Next-generation sequencing panels such as~~ FoundationOne CDx (324 genes~~) and~~ MSK-IMPACT (341 genes~~) enable comprehensive genomic profiling that identifies rare actionable mutations in 1–2% of cases, including ALK rearrangements responsive to targeted therapy~~. ~~For the 9–12% of mesothelioma patients carrying germline BAP1~~ mutations~~, genetic testing triggers cascade screening of family members and lifelong cancer surveillance, as these mutations confer a 30~~% ~~lifetime risk of~~ mesothelioma ~~along with elevated risks of uveal melanoma, renal cell carcinoma, and other cancers.~~<ref name="~~pmc_ngs_clinical~~" /><ref name="~~pmc_genetic_susceptibility~~" /><ref name="~~mlc_diagnosis~~" />		* '''CDKN2A FISH specificity''' — achieves 100% specificity for distinguishing malignant mesothelioma from benign mesothelial tissue<ref name="pubmed_bap1_cdkn2a" />
			* '''NF2/merlin inactivation''' — occurs in 30–40% of mesotheliomas with biallelic loss in 40% of TCGA-analyzed samples<ref name="pmc_nf2_alteration" />
			* '''CDKN2A deletion rate''' — homozygous deletion found in 45–74% of pleural and 25–35% of peritoneal mesotheliomas<ref name="nature_cdkn2a" />
			* '''Germline BAP1 mutations''' — present in 9–12% of pleural mesothelioma patients, conferring 7-fold improved 10-year survival (26% vs. sporadic)<ref name="pmc_bap1_germline_survival" />
			* '''NGS platform coverage''' — FoundationOne CDx analyzes 324 genes while MSK-IMPACT covers 341 cancer-associated genes<ref name="pmc_ngs_clinical" />
			* '''Tumor mutational burden''' — mesothelioma shows consistently low TMB at approximately 1.8 mutations per megabase across all subtypes<ref name="pmc_tmb" />
			* '''Liquid biopsy accuracy''' — cell-free DNA methylation profiling achieved 91% accuracy distinguishing mesothelioma from asbestos-exposed controls<ref name="asco_methylation" />
			* '''Rare actionable mutations''' — ALK fusions, KRAS G12C, and BRCA1/2 variants found in 1–2% of patients eligible for targeted therapy<ref name="pmc_ngs_clinical" />
			* '''PD-L1 expression''' — present at the ≥1% threshold in 20–50% of mesotheliomas but not validated as a reliable immunotherapy predictor<ref name="pmc_immunotherapy_biomarkers" />

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MesotheliomaSupport: Internal linking: added 2 wiki links

2026-02-20T21:01:41Z

Internal linking: added 2 wiki links

← Older revision		Revision as of 21:01, 20 February 2026
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	! colspan="2" style="background:#1a5276; color:white; padding:12px; font-size:1.1em; text-align:center;" \| Molecular & Genetic Testing		! colspan="2" style="background:#1a5276; color:white; padding:12px; font-size:1.1em; text-align:center;" \| Molecular & Genetic Testing
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	\| colspan="2" style="padding:10px; text-align:center; font-style:italic; border-bottom:1px solid #dee2e6;" \| Genomic Profiling for Mesothelioma		\| colspan="2" style="padding:10px; text-align:center; font-style:italic; border-bottom:1px solid #dee2e6;" \| Genomic Profiling for [[Mesothelioma]]
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	== Executive Summary ==		== Executive Summary ==

	Molecular and genetic testing has fundamentally transformed the diagnosis and management of malignant mesothelioma, moving the field beyond traditional histologic classification toward precision oncology approaches that match patients with targeted therapies and clinical trials. The three most clinically significant molecular alterations in mesothelioma are BAP1 loss (found in approximately 60% of pleural mesotheliomas), CDKN2A homozygous deletion (45–74% of pleural cases), and NF2 inactivation (30–40%), each providing both diagnostic and prognostic information that directly impacts patient care.<ref name="pmc_bap1_pleural" /><ref name="nature_cdkn2a" /><ref name="pmc_nf2_alteration" />		Molecular and genetic testing has fundamentally transformed the diagnosis and management of malignant mesothelioma, moving the field beyond traditional histologic classification toward precision oncology approaches that match patients with targeted therapies and [[Clinical Trials\|clinical trials]]. The three most clinically significant molecular alterations in mesothelioma are BAP1 loss (found in approximately 60% of pleural mesotheliomas), CDKN2A homozygous deletion (45–74% of pleural cases), and NF2 inactivation (30–40%), each providing both diagnostic and prognostic information that directly impacts patient care.<ref name="pmc_bap1_pleural" /><ref name="nature_cdkn2a" /><ref name="pmc_nf2_alteration" />

	BAP1 immunohistochemistry and CDKN2A fluorescence in situ hybridization represent the two most important ancillary tests for distinguishing malignant mesothelioma from reactive mesothelial proliferations, a diagnostic challenge that has historically delayed treatment. BAP1 IHC achieves 53% sensitivity with 86% specificity, while CDKN2A FISH achieves 41–61% sensitivity with 100% specificity — meaning a positive CDKN2A FISH result definitively confirms malignancy. When combined, these tests significantly improve diagnostic accuracy beyond either test alone.<ref name="pubmed_bap1_cdkn2a" /><ref name="pubmed_cdkn2a_cish" /><ref name="dandell_diagnosis" />		BAP1 immunohistochemistry and CDKN2A fluorescence in situ hybridization represent the two most important ancillary tests for distinguishing malignant mesothelioma from reactive mesothelial proliferations, a diagnostic challenge that has historically delayed treatment. BAP1 IHC achieves 53% sensitivity with 86% specificity, while CDKN2A FISH achieves 41–61% sensitivity with 100% specificity — meaning a positive CDKN2A FISH result definitively confirms malignancy. When combined, these tests significantly improve diagnostic accuracy beyond either test alone.<ref name="pubmed_bap1_cdkn2a" /><ref name="pubmed_cdkn2a_cish" /><ref name="dandell_diagnosis" />

MesotheliomaSupport: Create comprehensive molecular and genetic testing page: BAP1, CDKN2A, NF2, NGS, epigenetics, PD-L1, TMB

2026-02-20T04:49:21Z

Create comprehensive molecular and genetic testing page: BAP1, CDKN2A, NF2, NGS, epigenetics, PD-L1, TMB

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