Dataset Information

Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.

ABSTRACT: Rearrangements to the c-ros oncogene 1, receptor tyrosine kinase (ROS1) gene are reported in 1-2% of lung adenocarcinomas. These rearrangements are associated with a response to the small-molecule tyrosine kinase inhibitor crizotinib. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), which is considered the gold standard technique in detecting ROS1 rearrangements, and determining whether a patient would respond well to crizotinib treatment. However, FISH is an expensive and time-consuming assay, requiring specialized microscopy equipment and some level of technical expertise. The present report describes the case of a patient with advanced lung adenocarcinoma, who was identified to be negative for ROS-1 rearrangements by FISH, but positive by immunohistochemistry (IHC). The health of the patient improved following treatment with crizotinib. These results indicate that IHC assay could be an alternative option for the detection of ROS1 gene rearrangements.

SUBMITTER: Zhang N

PROVIDER: S-EPMC4214434 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.

Zhang Na N Yang Jin-Ji JJ Zhang Xu-Chao XC Xie Zhi Z Wang Bin-Chao BC Tu Hai-Yan HY Jiang Ben-Yuan BY Wu Yi-Long YL

Oncology letters 20140926 6

Rearrangements to the c-ros oncogene 1, receptor tyrosine kinase (ROS1) gene are reported in 1-2% of lung adenocarcinomas. These rearrangements are associated with a response to the small-molecule tyrosine kinase inhibitor crizotinib. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), which is considered the gold standard technique in detecting ROS1 rearrangements, and determining whether a patient would respond well to crizotinib tre ...[more]

PMID: 25364439

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Project description:BackgroundA subset of lung adenocarcinoma with EGFR-tyrosine kinase inhibitor sensitizing mutations (mEGFR) is common in non-smokers and women, suggesting that mutational stressors other than smoking are involved.MethodsTargeted sequencing using a custom panel containing 70 cancer-related genes were performed from 73 cases of lung adenocarcinoma with mEGFR (study cohort). In parallel, publicly available data of 47 TCGA-LUAD cases with mEGFR (LUAD cohort) were extracted from the GDC data portal and analyzed by non-negative matrix factorization using the Maftools package.ResultsIn the study cohort, the C?>?A transversions accounted for 12.9% of all single nucleotide variations (SNVs), comprising the second smallest proportion among SNVs. The E19del-subgroup had a significantly lower mutational burden with significantly higher Ti/Tv ratio than the SNV-subgroup, which includes cases with L858R and other EGFR-TKI sensitizing SNVs. (P?=?0.0326 and 0.0002, respectively, Mann-Whitney U test). In the LUAD cohort, the mutational burden was substantially lower than in other TCGA cancer cohorts, and the frequency of C?>?A transversions was 30.3%, occupying the second frequency. The E19del-subgroup had a lower mutational burden overall and a higher Ti/Tv ratio than the SNV-subgroup (P?=?0.0497 and P?=?0.0055, respectively, Mann-Whitney U test). Smoking-related signature 4 was observed only in the L858R-subgroup, while ignature 30 and 5 was observed in both groups.ConclusionsLung adenocarcinoma with mEGFR(+) has a lower mutational burden and does not show a characteristic mutation pattern influenced by smoking. E19del and L858R, which are representative subtypes of mEGFR(+) lung adenocarcinoma, differ in terms of mutational spectrum, as the E19del-subgroup has a lower mutation burden and a higher Ti/Tv ratio than the SNV-subgroup. These findings could help explain the differences in the responses to EGFR-TKIs and in the clinical courses between the two lung adenocarcinoma subgroups.

Dataset Information

Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.

Publications

Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.

Similar Datasets

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