Dataset Information

Rapid Autopsy in Thoracic Malignancy Cancer Patients to Investigate Tumor Heterogeneity

ABSTRACT:

Integrated proteo-genomics studies to characterize tumor heterogeneity of metastatic lung adenocarcinoma and thymic carcinoma are lacking. We carried out whole exome sequencing, RNA sequencing, copy number estimation and mass spectrometry-based proteomics of 40 tumors from five rapid/warm autopsy patients. We found highly variable mutational heterogeneity that was largely driven by APOBEC-mutagenesis with the expression of APOBEC3B (Gene ID: 9582) and APOBEC3A_B (Gene ID: 100913187) due to underlying APOBEC3 region germline variants as the likely mediating mechanism. APOBEC3A_B expression was associated with increased immune tumor microenvironment and CD274 (Gene ID: 29126) expression while smoking was associated with increased APOBEC-mutagenesis in TP53 (Gene ID: 7157) mutant tumors with high APOBEC3B expression. Heterogeneity at the level of the transcriptome and proteome occurred in association with copy number heterogeneity, not APOBEC-induced mutational heterogeneity. Arm and focal copy number alterations (CNAs) occurred as an evolutionarily late event in a subset of patients, with corresponding changes in the transcriptome and proteome, implicating CNAs as a driving force of heterogeneity in the evolution of metastatic disease.

PROVIDER: phs001432 | dbGaP |

SECONDARY ACCESSION(S): PRJNA398709PRJNA398710

REPOSITORIES: dbGaP

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Dataset's files

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			Action	DRS
	GapExchange_phs001432.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001432.AutopsyProcurement_ThoracicCancer.v1.p1.MULTI.pdf	Pdf
	manifest_phs001432.AutopsyProcurement_ThoracicCancer.v1.p1.c2.HMB-PUB.pdf	Pdf
	datadict_v2.xsl	Other

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Rapid Autopsy in Thoracic Malignancy Cancer Patients to Investigate Tumor Heterogeneity

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