ID
45751
Descrição
Principal Investigator: Udayan Guha, MD, PhD, National Institutes of Health, Bethesda, MD, USA MeSH: Adenocarcinoma of lung https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001159 We employed next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his seven year course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies demonstrated increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy due to L869R mutation and increased migration due to ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a sub-clone metastasized early from the primary site and evolved independently in lymph nodes.
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Versões (1)
- 05/06/2023 05/06/2023 - Chiara Middel
Titular dos direitos
Udayan Guha, MD, PhD, National Institutes of Health, Bethesda, MD, USA
Transferido a
5 de junho de 2023
DOI
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Licença
Creative Commons BY 4.0
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dbGaP phs001159 Genetic Analysis to Interrogate Tumor Heterogeneity in Lung Adenocarcinoma
Subject ID, consent group, subject source, source subject ID, and affection status of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- StudyEvent: SEV1
- Subject ID, consent group, subject source, source subject ID, and affection status of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- Subject ID, sample ID, sample source, source sample ID, and sample use variables obtained from participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- Sample ID, body site where sample was obtained, analyte type, tumor status, histological type, primary or metastatic tumor, primary tumor location, tumor stage, tumor grade, tumor treatment, genotyping center, and sequencing center of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
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Subject ID, consent group, subject source, source subject ID, and affection status of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- StudyEvent: SEV1
- Subject ID, consent group, subject source, source subject ID, and affection status of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- Subject ID, sample ID, sample source, source sample ID, and sample use variables obtained from participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
- Sample ID, body site where sample was obtained, analyte type, tumor status, histological type, primary or metastatic tumor, primary tumor location, tumor stage, tumor grade, tumor treatment, genotyping center, and sequencing center of participants with lung adenocarcinoma and involved in the "Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants" project.
C0441833 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,2])
C0681850 (UMLS CUI [1,3])
C3847505 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,3])