دورية أكاديمية
The genomic landscape of lung cancer in never-smokers from the Women's Health Initiative.
العنوان: | The genomic landscape of lung cancer in never-smokers from the Women's Health Initiative. |
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المؤلفون: | Moorthi S; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Paguirigan A; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Itagi P; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Ko M; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Pettinger M; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Hoge AC; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Nag A; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, United States of America., Patel NA; Center for Cancer Genomics, Dana Faber Cancer Institute, Boston, United States of America., Wu F; Shared Resources - Genomics, Fred Hutchinson Cancer Center, Seattle, United States of America., Sather C; Genomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America., Levine KM; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Fitzgibbon MP; Genomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Center, Seattle, United States of America., Thorner AR; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, United States of America., Anderson GL; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, United States of America., Ha G; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America., Berger AH; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America. |
المصدر: | JCI insight [JCI Insight] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25. |
Publication Model: | Ahead of Print |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
مستخلص: | Over 200,000 individuals are diagnosed with lung cancer in the U.S. every year, with a growing proportion of cases, especially lung adenocarcinoma, occurring in individuals who have never smoked. Women over the age of 50 comprise the largest affected demographic. To understand the genomic drivers of lung adenocarcinoma and therapeutic response in this population, we performed whole genome and/or whole exome sequencing on 73 matched lung tumor/normal pairs from post-menopausal women who participated in the Women's Health Initiative. Somatic copy number alterations showed little variation by smoking status, suggesting that aneuploidy may be a general characteristic of lung cancer regardless of smoke exposure. Similarly, clock-like and APOBEC mutation signatures were prevalent but did not differ in tumors from smokers and never-smokers. However, mutations in both EGFR and KRAS showed unique allelic differences determined by smoking status that are known to alter tumor response to targeted therapy. Mutations in the MYC-network member MGA were more prevalent in tumors from smokers. Fusion events in ALK, RET, and ROS1 were absent, likely due to age-related differences in fusion prevalence. Our work underscores the profound impact of smoking status, age, and sex on the tumor mutational landscape and identifies areas of unmet medical need. |
معلومات مُعتمدة: | R37 CA252050 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS; T32 CA009515 United States CA NCI NIH HHS; R01 CA284585 United States CA NCI NIH HHS; K22 CA237746 United States CA NCI NIH HHS; R01 CA262556 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: Genetic variation; Genetics; Lung cancer; Molecular diagnosis; Therapeutics |
تواريخ الأحداث: | Date Created: 20240725 Latest Revision: 20240828 |
رمز التحديث: | 20240828 |
DOI: | 10.1172/jci.insight.174643 |
PMID: | 39052387 |
قاعدة البيانات: | MEDLINE |
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