Dataset Information

Landscape of FGF/FGFR Alterations in 12,372 Chinese Cancer Patients.

ABSTRACT: Purpose: The aberrant of fibroblast growth factors and their receptors (FGF/FGFR) is an emerging target in the treatment of solid tumors. This study aimed to explore the landscape of FGF/FGFR alterations in a large cohort of cancer patients. Material and Methods: The formalin-fixed paraffin-embedded specimens of cancer patients who have underwent next-generation sequencing (NGS) from 2017 to 2019 in 3DMed Clinical Laboratory Inc. were included in this study. Findings: Of 12,372 Chinese cancer patients with more than 20 tumor types (60% male, median age, 58.0 [IQR, 49.0-66.0]), genomic alterations in FGF, FGFR, and both were observed in 895 (7.2%), 862 (7.0%), and 186 (1.5%) patients, respectively. The highest prevalence of FGF/FGFR mutations fell in esophagus cancer (61.6%, 98/159) and urinary tract cancer (52.7%, 145/275). The most common pathway-level mutations were FGFR single nucleotide variants (635, 5.1%) and FGF amplifications (628, 5.1%). The microsatellite instability status was negatively associated with amplifications (p=0.0017). Conclusion: FGF/FGFR alterations were widely occurred in cancer patients, and the mutational landscape may contribute to the further study design and development of FGF/FGFR inhibitors.

SUBMITTER: Zuo W

PROVIDER: S-EPMC7545692 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Landscape of FGF/FGFR Alterations in 12,372 Chinese Cancer Patients.

Zuo Wei W He Yan Y Li Wei W Wu Hao H Zhao Zhengyi Z Zhang Yuzi Y Chen Shiqing S Yin Yongmei Y

Journal of Cancer 20200923 22

Purpose: The aberrant of fibroblast growth factors and their receptors (FGF/FGFR) is an emerging target in the treatment of solid tumors. This study aimed to explore the landscape of FGF/FGFR alterations in a large cohort of cancer patients. Material and Methods: The formalin-fixed paraffin-embedded specimens of cancer patients who have underwent next-generation sequencing (NGS) from 2017 to 2019 in 3DMed Clinical Laboratory Inc. were included in this st ...[more]

PMID: 33046990

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Project description:PurposeTo analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world.MethodsWe analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones.ResultsThe proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD.ConclusionCompared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy.

Dataset Information

Landscape of FGF/FGFR Alterations in 12,372 Chinese Cancer Patients.

Publications

Landscape of <i>FGF</i>/<i>FGFR</i> Alterations in 12,372 Chinese Cancer Patients.

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