Dataset Information

Evolutionary Genome Analysis of Transformation into Small Cell Carcinomas from Lung Adenocarcinomas

ABSTRACT: Anecdotal case have been reported lung adenocarcinoma could occasionally transform into small cell carcinoma. Most of the reported cases were EGFR-mutant lung adenocarcinomas that transform into small cell carcinoma during EGFR tyrosine kinase inhibitor treatment. However, some cases also indicate lung adenocarcinomas without EGFR mutation could also transform into small cell carcinomas. Here we investigate this transformation process by whole genome sequencing of transformed small cell carcinomas as well as serially acquired samples of lung adenocarcinoma into small cell carcinomas.

PROVIDER: EGAS00001001757 | EGA |

REPOSITORIES: EGA

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Publications

Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas.

Lee June-Koo JK Lee Junehawk J Kim Sehui S Kim Soyeon S Youk Jeonghwan J Park Seongyeol S An Yohan Y Keam Bhumsuk B Kim Dong-Wan DW Heo Dae Seog DS Kim Young Tae YT Kim Jin-Soo JS Kim Se Hyun SH Lee Jong Seok JS Lee Se-Hoon SH Park Keunchil K Ku Ja-Lok JL Jeon Yoon Kyung YK Chung Doo Hyun DH Park Peter J PJ Kim Joon J Kim Tae Min TM Ju Young Seok YS

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20170512 26

Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at ...[more]

PMID: 28498782

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Project description:The success of targeted therapies creates a need to discriminate tumors accurately by their histological and genetic characteristics. Here, we used cDNA microarray analysis to identify gene expression profiles and single markers that recapitulate the pathological and genetic background (i.e., BRAF, EGFR, KRAS, LKB1, PIK3CA, and TP53 gene alterations) of non-small cell lung cancer (NSCLC). Gene expression profiles were determined for 6 normal lung tissues and 69 lung tumors from patients diagnosed with NSCLC. We performed an unsupervised hierarchical clustering with the most variably expressed transcript to investigate whether there was evidence for natural grouping samples based on similarity in gene expression profiles. We examined the relationship between the clusters of tumors and patient and tumor characteristics such as gender, smoking status, histological type, degree of differentiation, tumor size, lymph node involvement and genetic background. We used a supervised analysis to identify the genes that are important for distinguishing subgroups of tumors defined by histological type. Moreover, we used this supervised approach to search for markers that characterize those tumors carrying EGFR, KRAS, PIK3CA and TP53 alterations. We identify several genes with characteristic patterns of expression in each tumor histological type (adenocarcinoma and squamous cell carcinoma) and we found that the presence of EGFR mutations result in a particular expression profile. Keywords: Transciption profiling of tumors with different histological and genetic background. We analyzed 69 NSCLC tumors. All the samples were characterized by histological type and by the presence of alterations at genes that are known to be involved in lung carcinogenesis. Mutational analysis of BRAF, EGFR, KRAS, and LKB1 is provided only for adenocarcinomas and analysis of alterations at PIK3CA gene (mutational analysis or gene amplification by FISH analysis) is provided only for 47 of the tumors. We analyzed gene expression profiles to identify those genes that are differentially expressed between two subgroups by t-test: 1) adenocarcinomas vs. squamous cell carcinomas; 2) tumors with mutation at EGFR gene vs. wild type tumors; 3) tumors with mutation at KRAS gene vs. wild type tumors; 4) tumors with mutation at TP53 gene vs. wild type tumors; 5) tumors with alterations (mutation or gene amplification) at PIK3CA gene vs. wild type tumors.

Dataset Information

Evolutionary Genome Analysis of Transformation into Small Cell Carcinomas from Lung Adenocarcinomas

Publications

Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas.

Similar Datasets

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