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Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky.

ABSTRACT: BACKGROUND:Lung cancer is the leading cause of cancer mortality in the United States (U.S.). Squamous cell carcinoma (SQCC) represents 22.6% of all lung cancers nationally, and 26.4% in Appalachian Kentucky (AppKY), where death from lung cancer is exceptionally high. The Cancer Genome Atlas (TCGA) characterized genetic alterations in lung SQCC, but this cohort did not focus on AppKY residents. METHODS:Whole-exome sequencing was performed on tumor and normal DNA samples from 51 lung SQCC subjects from AppKY. Somatic genomic alterations were compared between the AppKY and TCGA SQCC cohorts. RESULTS:From this AppKY cohort, we identified an average of 237 nonsilent mutations per patient and, in comparison with TCGA, we found that PCMTD1 (18%) and IDH1 (12%) were more commonly altered in AppKY versus TCGA. Using IDH1 as a starting point, we identified a mutually exclusive mutational pattern (IDH1, KDM6A, KDM4E, JMJD1C) involving functionally related genes. We also found actionable mutations (10%) and/or intermediate or high-tumor mutation burden (65%), indicating potential therapeutic targets in 65% of subjects. CONCLUSIONS:This study has identified an increased percentage of IDH1 and PCMTD1 mutations in SQCC arising in the AppKY residents versus TCGA, with population-specific implications for the personalized treatment of this disease. IMPACT:Our study is the first report to characterize genomic alterations in lung SQCC from AppKY. These findings suggest population differences in the genetics of lung SQCC between AppKY and U.S. populations, highlighting the importance of the relevant population when developing personalized treatment approaches for this disease.

SUBMITTER: Liu J

PROVIDER: S-EPMC6363884 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky.

Liu Jinpeng J Murali Thilakam T Yu Tianxin T Liu Chunming C Sivakumaran Theru A TA Moseley Hunter N B HNB Zhulin Igor B IB Weiss Heidi L HL Durbin Eric B EB Ellingson Sally R SR Liu Jinze J Huang Bin B Hallahan Brent J BJ Horbinski Craig M CM Hodges Kurt K Napier Dana L DL Bocklage Thèrése T Mueller Joseph J Vanderford Nathan L NL Fardo David W DW Wang Chi C Arnold Susanne M SM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20181030 2

<h4>Background</h4>Lung cancer is the leading cause of cancer mortality in the United States (U.S.). Squamous cell carcinoma (SQCC) represents 22.6% of all lung cancers nationally, and 26.4% in Appalachian Kentucky (AppKY), where death from lung cancer is exceptionally high. The Cancer Genome Atlas (TCGA) characterized genetic alterations in lung SQCC, but this cohort did not focus on AppKY residents.<h4>Methods</h4>Whole-exome sequencing was performed on tumor and normal DNA samples from 51 lun ...[more]

PMID: 30377206

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Project description:BackgroundAppalachian Kentucky faces the highest cancer incidence and mortality rates in the country due to poor health behaviors and lifestyle choices. These poor health behaviors are facilitated by a lack of cancer education. Youth represent a vulnerable population that could be greatly impacted by increased cancer education. Teachers have the power to facilitate this learning.PurposeThis study examined the need for cancer education curriculum in Appalachian Kentucky middle and high schools from the perspective of educators.MethodsAn online survey was conducted with science and health teachers (n=21) in Appalachian Kentucky, consisting of questions that investigated existing cancer education efforts, relevance of cancer education, and feasibility of such curriculum being delivered in the classroom. Content analysis was used to analyze teacher comments. A 3-part cancer education curriculum was developed that is culturally relevant and aligned with science and health education standards.ResultsAll participating teachers agree that cancer education is important to students' lives. Teachers also agree that there is an inconsistent amount of cancer education within schools, and qualitative content analysis revealed that cancer education likely fits best in certain course subjects. Cancer education could feasibly be integrated into science and health classrooms, although the perception of needing to teach to the academic standards and having limited time to teach additional lessons outside of the standards are significant barriers. To combat this, a cancer curriculum that aligns with state and national science and health education standards was developed.ImplicationsCancer education curriculum could play an important role in improving the cancer outlook in Appalachian Kentucky. Teachers have expressed a desire for increased cancer education in the classroom. By disseminating and implementing cancer curriculum in schools in the region and revising the curriculum -based on teacher and student feedback to better fit their needs, it has the potential to increase cancer literacy and improve related health behaviors and outcomes.

Dataset Information

Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky.

Publications

Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky.

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