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High prevalence of ROS1 gene rearrangement detected by FISH in EGFR and ALK negative lung adenocarcinoma.

Exp Mol Pathol. 2020 Dec;117:104548. Epub 2020 Sep 24
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摘要


rearrangement has become an important biomarker for targeted therapy in advanced lung adenocarcinoma (LUAD). The study aimed to evaluate the prevalence of duanyu16701 rearrangement in Chinese LUAD with EGFR wild-type and ALK fusion-negative status, and analyze the relationship with their clinicopathological characteristics. A large cohort of 589 patients of LUAD with EGFR/ALK wild-type, diagnosed between April 2014 and June 2018, was retrospectively analyzed. duanyu16701 rearrangement in all these cases was detected by FISH, and 8 selected cases with different positive and negative signals were confirmed by NGS. As a result, total of 56 cases with duanyu16701 rearrangements out of 589 LUADs (9.51%) were identified by FISH. The frequency of duanyu16701 rearrangement in women was 22.15% (35/158), which was statistically higher than 4.87% (21/431) in men (P < 0.001). The duanyu16701 positive rate in the patients with age < 50 years old (25.29%, 22/87) was statistically higher than that in the patients with age ≥ 50 (6.77%, 34/502) (P < 0.001). There was a trend that the frequency of duanyu16701 rearrangement in LUAD with stage III-IV was higher than that in stage I-II (9.56%, 39/408 vs 2.50%, 1/40), although it did not reach significant difference (P = 0.135). 37 out of 56 cases of duanyu16701 rearranged LUAD showed solid (n = 20, 35.71%) and invasive mucinous adenocarcinoma (n = 17, 30.36%) pathological subtypes. The median OS for patients of duanyu16701 rearranged LUAD treated with TKIs (n = 29) was 49.69 months (95% CI: 36.71, 62.67), compared with 32.55 months (95% CI: 23.24, 41.86) for those who did not receive TKI treatment (n = 16) (P = 0.040). The NGS results on duanyu16701 rearrangement in all the 8 cases were concordant with FISH results. In conclusion, high prevalence of duanyu16701 rearrangements occurs in EGFR/ALK wild-type LUAD detected by FISH, especially in younger, female, late stage patients, and in histological subtypes of solid and invasive mucinous adenocarcinoma.

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