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Background/Aims: As targeted therapies are promising in the treatment of lung cancer (LC), it is important to identify the genetic variations in tumors. The present research aimed to determine the regional prevalence of alterations in ALK, ROS1, and EGFR genes. Materials and Methods: ALK rearrangement in 1152, ROS1 rearrangement in 390, and EGFR mutations in 1054 cases with LC were evaluated. Results: Alteration rates of ALK, ROS1, and epidermal growth factor receptor (EGFR) genes were 3.5%, 0.4%, and 11.2% in the samples, respectively. ALK rearrangements were mainly detected in young patients (P < 0.01) and in females (P < 0.01). Females were also more often inflicted by EGFR variations, especially from the exon 19 deletion. Exon 21 L858R mutations were more frequently found in men. However, any statistical significance between EGFR alterations and gender or age was not discovered. Conclusion: In this study, molecular changes were less frequent than expected. We thought that this low rate confirmed the aphorism of “smokes like a Turk, ” which could be because almost all patients were active or passive smokers.
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Background: Mutations in ROS1, ALK, and MET genes are targetable alterations in non-small cell lung cancer (NSCLC). They can be evaluated by different techniques, most commonly fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Methods: We explored the prevalence of ROS1, ALK, MET mutations, discuss clinicopathological associations and FISH signal patterns on 413 consecutive cases of EGFR negative lung carcinoma from March 2016 to April 2017 using FISH for ALK, ROS1, and MET along with ALK (D5F3) IHC. Results: ROS1 gene rearrangement, ALK positivity (IHC and/or FISH), and MET amplification were seen in 18/358 (5%) cases, 76/392 cases (19.4%), and 10/370 (2.7%) cases, respectively. ALK FISH and ALK IHC were positive in 51/300 (17%) and 58/330 cases (17.57%), respectively, while 8/330 (2.4%) cases were ALK IHC “equivocal” of which 3/8 (37.5%) were ALK FISH positive. Of ALK FISH and IHC co-tested cases, 43/238 (18.07%) cases were positive by both techniques, while 15/43 (34.88%) of ALK positive cases showed discordant ALK FISH and IHC results. All ROS1 rearranged and MET amplified cases were adenocarcinoma. Signet ring cell histology was associated with 78.57% likelihood of being either ALK or ROS1 positive. Genomic heterogeneity was seen in 30% of MET amplified cases. Conclusions: ALK/ROS1/MET gene alterations were found in 25.18% of NSCLC cases. An ALK IHC “equivocal” interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance.
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The incidence of ROS1 gene rearrangement/fusion in non-small cell lung cancer (NSCLC) is about 1%-2%. The advent of tar-geted drugs for ROS1 gene fusion has significantly improved the quality of life and total survival of NSCLC patients with ROS1 fusion;however, acquired drug resistance is still present in most patients after continuous treatment. This review has summarized the back-ground of the ROS1 fusion gene, detection method, clinical efficacy of ROS1-targeted therapy, and strategy and prospect of drug resis-tance.
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The molecular target therapy of non-small cell lung cancer (NSCLC) has become a hot research direction in the field of medicine.Following the discovery of well-known tumor-driven genes such as epidermal growth factor receptor (EGFR),Kirsten rat sarcoma viral oncogene (KRAS) and anaplastic lymphoma kinase (ALK) genes,more and more scholars have shifted focus to ROS1 fusion gene.The protein encoded by ROS1 is a member of the receptor tyrosine kinase super family,and it plays an important role in cell growth and cell survival.ROS1 fusion gene plays a vital role in the occurrence,development and clinical treatment of NSCLC.
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Purpose The aim was to examine c-MET,ALK,ROS1 variants in advanced non-small cell lung cancer (NSCLC) patients,and to analysis the association of c-MET,ALK,ROS1 variants with the clinical and pathological features.Methods The c-MET,ALK,ROS1 were detected by fluorescence in situ hybridization (FISH) in the 91 cases of NSCLC specimens.The correlation of c-MET gene amplification with clinicopathological features and the ALK,ROS1 fusions was analyzed.Results The positive rate of c-MET gene amplification was 8.79％ (8/91),the positive rates on male and female were 1.82％ and 19.4％,respectively.In ＜ 60-years-old and ≥60-years-old NSCLC patients,the positive rates were 7.5％ and 8.89％,resepectively.The positive rate was higher in stage Ⅲ than stage Ⅳ (9.62％ vs 7.69％),the c-MET gene amplification was detected in 9.2％ adenocarcinoma patients but none in squamous carcinoma patients.The detection rates of ALK fusions and ROS1 fusions were 10％ and 13.3％,respectively.One patient was detected the coexistence of MET with ROS1 fusion.Conclusion The c-MET gene amplification is correlated with gender,but not with age,histological types and clinical stages.C-MET amplification,ALK fusions and ROS1 fusions are almost no coexistence,but not completely mutually exclusive.To they knowledge,this is the first case report the coexistence of MET amplification with ROS1 fusion in NSCLC.
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Objective To investigate the characteristics of EGFR,ALK and ROS1 mutations in patients with non-small cell lung cancer (NSCLC) in South of China and its relationship with clinical features.Methods The tumor tissues and corresponding clinical data of 76 NSCLC patients in South of China from November 2016 to June 2017 were collected.The mutations of EGFR,ALK and ROS1 were detected by ARMS assay with Joint detection kit.Meanwhile,the correlation between gene mutation rate and clinical features was analyzed.Results The mutation rate of EGFR was 67.3％ (42/76) in 76 patients with NSCLC in South of China,19 del and L858R mutations were the main mutation types.There was a co-mutation including 19 del and L858R.The positive rate of ALK gene fusion was 17.1％ (13/76),and 4 cases of ALK gene fusion combined with EGFR mutation were detected.The positive rate of ROS1 gene fusion was 1.3％ (1/76),and there was no co-mutation with other genes.Compared with ROS1,EGFR and ALK mutation rate was higher,the difference was statistically significant (x2 =54.515,P =0.000;x2 =11.329,P =0.001).The mutation rate of EGFR in non-smoking NSCLC patients was significantly higher than that in smokers (x2 =4.578,P=0.032),while the mutation rate of ALK and ROS1 was not statistically significant (x2=0.000,P＞0.05).There was no statistically significant difference in EGFR,ALK and ROS1 gene mutation rates among NSCLC patients of different age,sex and histology (x2 =0.000 ～ 2.219,P＞ 0.05).Conclusion EGFR,ALK and ROS1 gene mutations can be seen in patients with NSCLC in South China,in which EGFR and ALK gene mutation rate is higher.
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Purpose To investigate the mutation rate of EGFR,KRAS,ALK and ROS1 in non-small cell lung cancer (NSCLC) and its association with clinical or pathological characteristics.Methods 86 NSCLC tissues were included.Fluorescence PCR was used to detect the EGFR,KRAS mutation and ALK,ROS1 fusion gene.The association between EGFR,KRAS,ALK and ROS1 gene and age,gender,smoking history,histological type,lymph node metastasis and other clinical pathological features were analyzed.Results The total mutation rate of the driver gene in NSCLC patients was 62.8％ (54/86).EGFR mutation rate was 76％ (41/54).KRAS mutation rate was 9.3％ (5/54).ALK gene fusion mutation rate was 13.0％ (7/54),and in one of the patients,EGFR 19 deletion mutation and ALK fusion co-exist.ROS1 gene fusion mutation was 3.8％ (2/54).EGFR gene mutation rate was higher in adenocarcinoma and female (P ＜ 0.05),but no significant association was found in age,smoking history and lymph node metastasis (P ＞0.05).KRAS,ALK,ROS1 genes had no obvious correlation with clinical pathological features (P ＞ 0.05).Conclusion The EGFR mutation and ALK fusion was rather high in patients with NSCLC.More attention should be paid to them.Though KRAS,ROS1 mutations and double mutations were low in NSCLC patients,they should not be ignored.
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PURPOSE: The recent discovery and characterization of an oncogenic ROS1 gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). MATERIALS AND METHODS: A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. RESULTS: Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)–negative patients compared with ROS1 IHC–positive patients. ROS1 FISH–positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between ROS1-positive and -negative patients. CONCLUSION: ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
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Humans , Cholangiocarcinoma , Fluorescence , Gene Rearrangement , Immunohistochemistry , In Situ Hybridization , In Situ Hybridization, Fluorescence , IncidenceABSTRACT
With the development of the pathogenesis and biological behavior in NSCLC ,the treatment of targeted relevant molecular has became a key method .ROS1 has been identified in a subset of non -small cell lung cancer ( NSCLC ) .The fusion gene is most often detected in non -smokers with lung adenocarcinoma and performs unique pathologic features .ROS1 fusion gene is an oncogenie ,which could be suppressed by ALK -in-hibitor through blocking the downstream signaling pathway of ROS 1.Therefore,ROS1 fusion gene may become a new targeted treatment followed by the EGFR and ALK -EML4.This review focuses on the molecular structure , function,biology,detection method and the diagnostic and therapeutic meanings of ROS 1 of lung cancer.
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Many attempts have been made to find genetic abnormalities inducing carcinogenesis after the development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor targeting EGFR in lung cancer. New target therapies have been already commercialized and studied along with the recent discovery of gene rearrangement involved in the carcinogenic process of non-small cell lung cancer. This study aims to investigate anplastic lymphoma kinase, c-ros oncogene 1, and receptor tyrosine kinase, in particular.
Subject(s)
Carcinogenesis , Carcinoma, Non-Small-Cell Lung , Gene Rearrangement , Lung Neoplasms , Lung , Lymphoma , Oncogenes , Phosphotransferases , Protein-Tyrosine Kinases , ErbB ReceptorsABSTRACT
PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.