Dataset Information

Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene.

ABSTRACT: OBJECTIVES:Since no report on the genetic characteristics of RET fusions in female patients with lung cancer is available, this study revealed the genetic and prognostic characteristics of female patients with lung cancer harboring RET fusion gene for the first time. MATERIALS AND METHODS:The molecular portfolios of 1,652 patients with lung cancer who underwent targeted next-generation sequencing for screening candidate oncogenic drivers in their histological specimens from January 2016 to December 2018 were investigated in this study. RESULTS:RET fusions were identified in 23 cases, 15 females [2.2% (15/685)] and eight males [0.9% (8/902)]. The most common fusions were KIF5B-RET in females [80% (12/15)] and CCDC6-RET in males [50% (4/8)], along with some rare RET fusions, including SLC39A8-RET, ITIH2-RET, FYCO1-RET and SLC25A36-RET in females, and MIR3924-RET, ZBTB41-RET and ITGA8-RET in males. Interestingly, the highly positive, moderate positive, and negative rates of PD-L1 staining in females were 33.3%, 8.3% and 58.3%, respectively; whereas those in males were 0%, 57.1% and 42.9%. Additionally, the progression-free survival (PFS) of stage IV patients was comparatively shorter in females, shown by the medians of 4.0 months in females and 6.0 months in males (P?=?0.029). A 43-year-old female patient with metastatic lung adenocarcinoma, who harbored KIF5B-RET fusion and had highly positive PD-L1 staining, received nivolumab as second-line treatment. A partial response was achieved and remained for more than five months. CONCLUSION:Unique genetic characteristics and poor prognosis are found in female patients with lung cancer harboring RET fusion gene. Immune checkpoint inhibitors are a potential option for patients with high expression of PD-L1.

SUBMITTER: Qiu Z

PROVIDER: S-EPMC7316706 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene.

Qiu Zhixin Z Ye Bingwei B Wang Ke K Zhou Ping P Zhao Shuang S Li Weimin W Tian Panwen P

Scientific reports 20200625 1

<h4>Objectives</h4>Since no report on the genetic characteristics of RET fusions in female patients with lung cancer is available, this study revealed the genetic and prognostic characteristics of female patients with lung cancer harboring RET fusion gene for the first time.<h4>Materials and methods</h4>The molecular portfolios of 1,652 patients with lung cancer who underwent targeted next-generation sequencing for screening candidate oncogenic drivers in their histological specimens from Januar ...[more]

PMID: 32587276

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Project description:Background The incidence of lung cancer is growing fast in China, however, the prognosis remains dismal due to the limited therapeutic approaches. The “ret proto-oncogene mutation” (RET) fusions have been proven to be the driver gene in lung cancer development and the therapeutic target of several multi-target tyrosine kinase inhibitors. Methods We applied formalin-fixed, paraffin-embedded (FFPE) samples of 39 patients with non-small cell lung cancer (NSCLC) using the Lung Plasma panel covering 168 cancer-associated genes and performed capture-based targeted deep sequencing to identify the RET fusion partners and concurrent gene mutation with Miseq. The log-rank test was used to compare the survival difference of patients according to treatment strategies. Statistical analyses and graphs were performed using R language and GraphPad Prism. Results Most of the samples were advanced (stage IIIb and IV) lung adenocarcinomas (80.77%). KIF5B-RET fusions were identified in 52% of the samples and K15-E12 was the most common variant. 6 (15%) samples harbored concurrent TP53 mutation and 3 samples were positive with EGFR mutation including a mutation in exon 19. Of these patients included, ten received cabozantinib, two received anlotinib, and one received crizotinib. Two (20%; 0–45) samples achieved stable disease and two were progressed in the cabozantinib treated group. Median progression-free survival (PFS) was 4 months (95% CI: 3.2–4.8) and median overall survival (OS) was 25 months (95% CI: 1.5–48.5). Three (11.54%; 0–24) samples achieved partial response in patients without RET inhibitor treatment and 4 (15.38%; 2–29) were stable disease. The median PFS was 11 months (95% CI: 1.2–20.8). There was no significant difference in PFS and OS between groups with or without RET inhibitors treatment. Conclusion This study provided insight into the RET fusions patients treatment. The survival benefit of current RET inhibitors was limited. More precise and potent RET inhibitors should be developed in the near future.

Project description:BackgroundRearranged during transfection (RET) is a targetable oncogene. RET fusions have been reported in patients with metastatic colorectal cancer (mCRC). However, RET mutations in mCRC are less studied. Here, we aimed to characterize the clinical, pathological, and molecular landscape of RET-mutated mCRC.MethodsFive hundred and eighty-two patients were included in this study. Next-generation sequencing was performed to detect RET mutations and calculate tumor mutation burden (TMB). We compared the clinical, pathological, and molecular characteristics of mCRC cases with tumors that harbored somatic RET mutations (N = 16, 2.7%) or had wild-type RET (N = 566, 97.3%).ResultsMales comprised the absolute majority of cases with RET mutations (15/16 [93.8%]) compared to their fraction among cases with wild-type RET (339/566 [59.9%]). Furthermore, all patients with RET mutations were younger than 60 years (16/16 [100%]), whereas such patients were less predominant in the group with wild-type RET (379/566 [67.0%]). Individuals with tumors positive for RET mutations more frequently exhibited mucinous histology (5/16 [31.2%] vs. 55/566 [9.7%]), exhibited a lower incidence of liver metastasis (4/16 [25.0%] vs. 335/566 [59.2%]), and higher incidence of peritoneal metastasis (9/16 [56.2%] vs.161/566 [28.4%]), expressed wild-type TP53 (8/16 [50.0%] vs.120/566 [21.2%]), and showed an increased frequency of MSI-high (6/16 [37.5%] vs. 18/566 [3.2%]). In those with microsatellite-stable mCRC, patients with RET mutations had a higher median TMB than patients with wild-type RET (9.4 vs. 6.7 mutations/Mb, respectively, p = 0.001). The median progression-free survival was similar in individuals with mutated and wild-type RET on the oxaliplatin-based regimen (7.1 vs. 8.7 months, p = 0.516).ConclusionsOur study suggests that cases with RET mutations represent a separate mCRC subtype. Further studies are needed to evaluate the efficacy of RET inhibitors in mCRC patients with RET mutations.

Dataset Information

Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene.

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Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene.

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