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Genomic alterations in tumor tissue and ctDNA from Chinese pancreatic cancer patients.
Xiong, Anwen; Ma, Ning; Wei, Guo; Li, Chunhua; Li, Kainan; Wang, Bin.
Afiliación
  • Xiong A; Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai 200438, P. R. China.
  • Ma N; Department of Clinical Laboratory, 905th Hospital of PLA 1328 Huashan Road, Shanghai 200050, P. R. China.
  • Wei G; Department of General Surgical, Changhai Hospital, Second Military Medical University 168 Changhai Road, Shanghai 200433, P. R. China.
  • Li C; Department of Oncology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jingba Road #1, Jinan 250001, Shandong, P. R. China.
  • Li K; Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University 11 Wuyingshan Middle Road, Jinan 250031, Shandong, P. R. China.
  • Wang B; Department of Oncology, Changhai Hospital, Second Military Medical University 168 Changhai Road, Shanghai 200433, P. R. China.
Am J Cancer Res ; 11(9): 4551-4567, 2021.
Article en En | MEDLINE | ID: mdl-34659905
ABSTRACT
Though the genomic feature of pancreatic cancer has been comprehensively studied in western patients, the genetic feature of Chinese patients is poorly clarified. In this study, a total of 225 pancreatic cancer patients were enrolled, mainly pancreatic ductal adenocarcinoma (PDAC, 97.33%). 140 patients (62.22%) provided sufficient tumor tissues for genomic analysis, and the rest (37.78%) were provided serum instead. Utilizing target next-generation sequencing (NGS), we analyzed genomic alterations of 618 selected genes. Corresponding data in the TCGA database were also analyzed here. In total, 26 (11.61%) patients had pathogenic or likely pathogenic germline variants, mainly (84.62%) involved genes in the DNA damage repair (DDR) pathway. The mean and median counts of somatic alterations per sample were 6.28 and 5, respectively. The most frequently mutated genes in our cohort were KRAS, TP53, CDKN2A, SMAD4, FBXW7 and ARID1A, revealing a significantly different prevalence of genes including KRAS, CDKN2A, ARID1A, NOTCH1, ARID1B than the corresponding data in the TCGA database. 39.11% of patients were identified with actionable alteration and the ratio was not significantly different between tissue and serum samples. 22.67% of patients harbored DDR gene alterations, which were associated with a higher tumor mutation burden. We also found that all the DDR alterations were not correlated with the overall survival and immune and stroma score, but the changes in NK cells and follicular T cells were identified in samples with DDR changes according to TCGA database. In summary, we identified a distinct genomic feature of Chinese pancreatic cancer patients by comparing with the data in TCGA database, and suggested the role for genetic testing using tissue or ctDNA samples in decision-making process. DDR alterations were associated with a higher tumor mutation burden and the significantly higher counts of NK cells in DDR altered samples may raise the attention in future related drugs development.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Am J Cancer Res Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Am J Cancer Res Año: 2021 Tipo del documento: Article