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Comprehensive analysis of age-related somatic mutation profiles in Chinese young lung adenocarcinoma patients.

ABSTRACT: BACKGROUND:Lung adenocarcinoma in young adults is a rare entity with the oncogenic genetic alterations associated being poorly understood. In the present study, the effect of genetic alterations in lung adenocarcinoma patients diagnosed in young patients is reported. METHODS:Twenty young lung adenocarcinoma patients (age years: median: 33.5, range: 24-36) were enrolled in the current study and 24 patients who were at common age of the disease onset (age years: median: 61.5, range: 52-79) were selected for comparison. Paraffin sections of lung adenocarcinoma were analyzed using the whole-exome sequencing platform. RESULTS:Similar number of somatic mutations per tumor were found in the young patients and their older counterparts. Although no age-related differences were detected in the numbers of lung adenocarcinoma patients harboring well-known gene variants, mutations in FRG1 and KMT2C were associated with a younger age especially after correcting for tobacco smoking and sex (FRG1: P = 0.027, KMT2C: P = 0.046). Five genetic variants showed higher alteration frequencies in young patients compared to the unclassified East Asian population, suggesting these mutations as disease-related hereditary germline variants. CONCLUSIONS:These results suggest different characteristics of lung adenocarcinoma between the young and the patients at common age of onset. Young patients with lung adenocarcinoma have a distinctly unique prevalence of oncogenic genetic alterations.

SUBMITTER: Yang B

PROVIDER: S-EPMC6488136 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Comprehensive analysis of age-related somatic mutation profiles in Chinese young lung adenocarcinoma patients.

Yang Bo B Li Jie J Li Fang F Zhou Hongxia H Shi Weiwei W Shi Huaiyin H Sun Shengjie S Sun Wending W Wang Jinliang J Ma Junxun J Yan Xiang X Hu Yi Y Jiao Shunchang S

Cancer medicine 20190301 4

<h4>Background</h4>Lung adenocarcinoma in young adults is a rare entity with the oncogenic genetic alterations associated being poorly understood. In the present study, the effect of genetic alterations in lung adenocarcinoma patients diagnosed in young patients is reported.<h4>Methods</h4>Twenty young lung adenocarcinoma patients (age years: median: 33.5, range: 24-36) were enrolled in the current study and 24 patients who were at common age of the disease onset (age years: median: 61.5, range: ...[more]

PMID: 30821106

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Project description:BACKGROUND:Occurrence at a younger age has been demonstrated to be associated with a distinct biology in non-small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next-generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma. MATERIALS AND METHODS:Seventy-one surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinicopathologic characteristics of 106 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively. RESULTS:The frequencies of targetable genetic alterations in 177 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of ALK and HER2 genetic alterations were associated with young age. However, a reverse trend was observed for KRAS, STK11 and EGFR exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent EGFR/TP53 mutations were much more prevalent in the younger patients (81.6% vs. 46.8%), which might have a poor response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor. CONCLUSION:In this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population. IMPLICATIONS FOR PRACTICE:Further investigation is needed to understand the genomics and clinical characteristics of young patients with lung adenocarcinoma. In the present study, hybrid capture-based next-generation sequencing assays were used to identify targeted genetic alterations in young lung adenocarcinoma patients. Young patients with lung adenocarcinoma, aged less than 45 years, harbored a higher frequency of ALK and HER2 genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent EGFR/TP53 mutations were much more prevalent in younger patients, which had a poor response to treatment with epidermal growth factor receptor kinase inhibitor. These results reveal a distinctive genetic profile in younger patients with adenocarcinoma, which might improve the treatment of this subpopulation.

Dataset Information

Comprehensive analysis of age-related somatic mutation profiles in Chinese young lung adenocarcinoma patients.

Publications

Comprehensive analysis of age-related somatic mutation profiles in Chinese young lung adenocarcinoma patients.

Similar Datasets

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