High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults

Scarpino, Stefania; Vinciguerra, Gian Luca Rampioni; Napoli, Arianna Di; Fochetti, Flavio; Uccini, Stefania; Iacono, Daniela; Marchetti, Paolo; Ruco, Luigi

doi:10.1016/j.lungcan.2016.04.022

Cited by 32 publications

(37 citation statements)

References 16 publications

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“…ROS1 and RET translocations reportedly are detected in <2% of patients with NSCLC and are identified predominantly in younger patients with adenocarcinoma who have no smoking history. 5,6,22,34 Surprisingly, ROS1 or RET translocations were identified in 4 of the 9 screened 5-wt patients aged 40 years. Together, when limiting the analysis to patients with EGFR/ ALK/KRAS wild-type adenocarcinomas and further focusing on the younger population, HER2 mutations and ROS1 and RET translocations are not "rare" oncogenic GAs, and patients should be routinely screened for these GAs, because matched, targeted therapies are currently promising for prolonging prognosis.…”

Section: Discussionmentioning

confidence: 97%

“…Histologic subtypes of lung adenocarcinoma were determined in 853 patients who underwent surgery, including 22 patients (3%) with adenoma in situ (AIS), 78 (9%) with minimally invasive adenocarcinoma (MIA), 50 (6%) with lepidic predominant adenocarcinoma, 269 (32%) with acinar predominant adenocarcinoma, 242 (28%) with papillary predominant adenocarcinoma, 23 (3%) with micropapillary predominant adenocarcinoma, 106 (13%) with solid predominant adenocarcinoma, and 63 (7%) with invasive mucinous adenocarcinoma (IMA). Among the 81 younger patients who had adenocarcinoma diagnosed at age 40 years, 36 (44%) were men, 36 (44%) were never smokers, and their median age was 36 years (range, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Original Article years). Patients with stage IV disease were significantly more frequent in this group compared with the older age group (aged >40 years; P < .001).…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma

Tanaka

Hida

Oya

et al. 2017

Cancer

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Section: Discussionmentioning

confidence: 97%

Section: Patient Characteristicsmentioning

confidence: 99%

Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma

Tanaka

Hida

Oya

et al. 2017

Cancer

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“…In a recent study on 727 lung adenocarcinomas from patients with stage IV disease, ROS1 fusions were independently associated with female sex, younger age at diagnosis and absence of smoking history 59. Compared with ALK -positive adenocarcinoma, the ROS-1 positive counterpart is more significantly associated with a peripheral location 60–62…”

Section: Introductionmentioning

confidence: 99%

Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives

Rossi¹,

Jocollè

Conti³

et al. 2017

LCTT

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ROS1 rearrangement characterizes a small subset (1%–2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer.

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“…These fusion events, which can involve a variety of partner genes, result in the formation of chimeric fusion kinases capable of oncogenic transformation and the induction of oncogene dependency within neoplastic cells. The individual prevalence of each of these chromosomal rearrangements ranges from 1% to 7% in NSCLC, and, together, these rearrangements can be identified in approximately 5%‐9% of NSCLC . Lung cancers harboring these fusion genes show oncogene addiction to the respective fusion genes and are therefore sensitive to treatment with tyrosine kinase inhibitors (TKI), such as crizotinib, alectinib (CH5424802), and ceritinib (LDK378).…”

Section: Introductionmentioning

confidence: 99%

“…1% to 7% in NSCLC, 4,6,9,10 and, together, these rearrangements can be identified in approximately 5%-9% of NSCLC. 7,11,12 Lung cancers harboring these fusion genes show oncogene addiction to the respective fusion genes and are therefore sensitive to treatment with tyrosine kinase inhibitors (TKI), such as crizotinib, alectinib (CH5424802), and ceritinib (LDK378).…”

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confidence: 99%

Performance of Oncomine Fusion Transcript kit for formalin‐fixed, paraffin‐embedded lung cancer specimens

et al. 2019

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Gene fusions play an important role in the carcinogenesis of lung adenocarcinoma. The recent association of four oncogenic driver genes, ALK , ROS1 , RET , and NTRK1 , as lung tumor predictive biomarkers has increased the need for precision medicine. We used formalin‐fixed, paraffin‐embedded tissue samples of non‐small cell lung cancer from 150 EGFR mutation‐negative cases and 10 fusion status‐known cases and compared the performance of the Oncomine Dx Fusion Transcript Test (ODxFT) with FISH break‐apart for the detection of ALK , RET , and ROS1 fusion genes. RNA was extracted from the paraffin‐embedded tissue samples with or without macrodissection under hematoxylin and eosin staining, and the ALK fusion gene was independently determined using these assays. Fusion detection analyses were successfully carried out using ODxFT in 150 cases, with only one invalid case. ALK fusion genes were detected at a frequency of 7.3% (11/150) in the lung cancer specimens. Concordance rate between the ODxFT and ALK ‐FISH analyses was 99.3% (148/149). Sensitivity and specificity were 91.7% and 99.3%, respectively. All the samples with a known fusion status were accurately matched between the two assays. Our results show a high concordance rate between the ODxFT and ALK ‐FISH analyses. ODxFT was thus validated as an effective method for detecting clinically significant ALK fusion genes in paraffin‐embedded tissue samples.

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High prevalence of ALK+/ROS1+ cases in pulmonary adenocarcinoma of adoloscents and young adults

Cited by 32 publications

References 16 publications

Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma

Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma

Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives

Performance of Oncomine Fusion Transcript kit for formalin‐fixed, paraffin‐embedded lung cancer specimens

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