Dataset Information

Characterization of the genomic landscape in large-scale Chinese patients with pancreatic cancer.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with an extremely poor prognosis. Effective targets for anticancer therapy confirmed in PDAC are limited. However, the characteristics of genomics have not been fully elucidated in large-scale patients with PDAC from China.

Methods

We collected both blood and tissue samples from 1080 Chinese patients with pancreatic cancer and retrospectively investigated the genomic landscape using next-generation sequencing (NGS).

Findings

We found recurrent somatic mutations in KRAS (83.2%), TP53 (70.6%), CDKN2A (28.8%), SMAD4 (23.0%), ARID1A (12.8%) and CDKN2B (8.9%) in Chinese PDAC patients. Compared with primary pancreatic cancers, more genomic alterations accumulated especially cell cycle regulatory gene variants (45.4% vs 31.6%, P < 0.001) were observed in metastatic tumors. The most common mutation site of KRAS is p.G12D (43.6%) in pancreatic cancer. Patients with KRAS mutations were significantly associated with older age and mutations in the other three driver genes, while KRAS wild-type patients contained more fusion mutations and alternative mechanisms of RTK/Ras/MAPK pathway including a number of clinically targetable mutations. KRAS mutations in Chinese cohort were significantly lower than those in Western cohorts (all P < 0.05). A total of 252 (23.3%) patients with the core DNA damage response (DDR) gene mutations were detected. ATM (n =59, 5.5%) was the most frequent mutant DDR gene in patients with pancreatic cancer from China. Patients with germline DDR gene mutations were younger (P = 0.018), while patients with somatic DDR gene mutations were more likely to accumulate in metastatic lesions (P < 0.001) and had higher TMB levels (P < 0.001). In addition, patients with mutant DDR genes and patients carrying TP53 mutation were observed mutually exclusive (P < 0.001).

Interpretation

We demonstrated the real-world genomic characteristics of large-scale patients with pancreatic cancer from China which may have promising implications for further clinical significance and drug development.

Funding

The funders are listed in the Acknowledgement.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8886010 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Characterization of the genomic landscape in large-scale Chinese patients with pancreatic cancer.

Zhang Xiaofei X Mao Tiebo T Zhang Bei B Xu Haiyan H Cui Jiujie J Jiao Feng F Chen Dongqin D Wang Yu Y Hu Jiong J Xia Qing Q Ge Weiyu W Li Shumin S Yue Ming M Ma Jingyu J Yao Jiayu J Wang Yongchao Y Wang Yanling Y Shentu Daiyuan D Zhang Xiao X Chen Shiqing S Bai Yuezong Y Wang Yuexiang Y Zhang Xuebin X Liu Qiang Q Sun Yongwei Y Fu Deliang D Liu Yingbin Y Xiong Lei L Wang Liwei L

EBioMedicine 20220226

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with an extremely poor prognosis. Effective targets for anticancer therapy confirmed in PDAC are limited. However, the characteristics of genomics have not been fully elucidated in large-scale patients with PDAC from China.<h4>Methods</h4>We collected both blood and tissue samples from 1080 Chinese patients with pancreatic cancer and retrospectively investigated the genomic landscape using next-generation sequencing ...[more]

PMID: 35231699

Similar Datasets

Project description: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.

Dataset Information

Characterization of the genomic landscape in large-scale Chinese patients with pancreatic cancer.

Background

Methods

Findings

Interpretation

Funding

Publications

Characterization of the genomic landscape in large-scale Chinese patients with pancreatic cancer.

Similar Datasets

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