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. 2025 May 5:1-17.
doi: 10.1159/000545560. Online ahead of print.

Real-World Genomic Landscape of Gastrointestinal Cancers in Asia and the Middle East Using Comprehensive Circulating Tumor DNA Next-Generation Sequencing

Manabu Muto  1 , Yu Sunakawa  2 , Nippun Sandhir  3 , Yi Hsin Liang  4 , Shaheenah Dawood  5 , Nitesh Rohatgi  6 , Ankur Bahl  6 , Steve Olsen  3
Affiliations

Real-World Genomic Landscape of Gastrointestinal Cancers in Asia and the Middle East Using Comprehensive Circulating Tumor DNA Next-Generation Sequencing

Manabu Muto et al. Oncol Res Treat. .

Abstract

Introduction: Gastrointestinal malignancies account for 25% of all cancer cases and 35% of cancer-related mortality. Next-generation sequencing (NGS) can elucidate the genomic landscape of gastrointestinal cancers; tissue-based genotyping has traditionally been used, but liquid biopsy-based genotyping is a noninvasive alternative. Moreover, geographical variations in the genomic landscape of gastrointestinal cancers have not been fully elucidated. This retrospective study aimed to gain insight into the genomic landscape of patients with gastrointestinal cancers from the Asia and Middle East (AME) region using plasma-derived circulating tumor DNA (ctDNA).

Methods: From routine clinical practice, 2,601 plasma samples were collected from 2,062 patients with gastrointestinal cancers in the AME region. NGS profiling was conducted using the Guardant360® assay. The frequency of biomarkers that can aid decision-making in cancer patients was investigated.

Results: Single-nucleotide variants affected most commonly TP53 (70.4%), KRAS (44.0%), APC (25.7%), ATM (15.1%), and PIK3CA (12.3%). Copy number alterations were most often observed in EGFR (13.7%), CCNE1 (5.9%), PIK3CA (5.0%), MYC (4.7%), and FGFR1 (4.6%); fusions were detected in 1.6% of patients and most frequently affected FGFR2, RET, ALK, FGFR3, and NTRK1/3. In patients with pancreatic adenocarcinoma, the most frequently observed clinically informative genomic biomarkers occurred in KRAS (G12C, 1.6%; all others, 67.1%), BRCA1/2 (4.1%), BRAF (V600X, 1.5%), and microsatellite instability-high (MSI-H) (1.0%). In patients with colorectal cancer, the most common clinically relevant alterations were KRAS (49.0%), BRAF (V600E, 7.6%), and NRAS (5.7%) mutations; ERBB2 amplifications (2.5%); and MSI-H (1.8%). In patients with biliary tract cancers, actionable alterations included IDH1 mutations (11.1%), ERBB2 amplifications (4.6%), FGFR2 fusions (2.0%), MSI-H (2.0%), and BRAF V600E (1.5%). In patients with gastric or gastroesophageal junction adenocarcinomas, actionable alterations included ERBB2 amplifications (10.1%) and MSI-H (3.6%).

Conclusion: Our data provide insight into the genomic landscape of patients with gastrointestinal cancers from the AME region using ctDNA analysis. These findings highlight the potential utility of liquid biopsy as a noninvasive tool for characterizing tumor genomic profiles and support its role in clinical practice.

Keywords: Circulating tumor DNA; Gastrointestinal cancers; Genomic landscape; Liquid biopsy.

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Conflict of interest statement

M.M. declares collaborations with Chugai, Taiho, NTT, PRiME-R, Canon Medical, Intage Healthcare, HU holdings, NTT data, XCOO, and Meiji Seika Pharma and being an invited speaker for Novartis, Daiichi Sankyo, MSD, Shionogi, Yakult, Merck, and Takeda. Y.S. declares research funding from Chugai Pharmaceutical Co., Ltd. and Taiho Pharmaceutical Co., Ltd.; honoraria from Eli Lilly Japan K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., MSD K.K., Novartis Pharmaceuticals, Astellas Pharma Inc., Sysmex, and Guardant Health; and participation on a Data Safety Monitoring Board or Advisory Board for Merck Biopharma Co., Ltd., Ono Pharmaceutical Co., Ltd., and Guardant Health. N.S. and S.O. declare employment at Guardant Health AMEA, Inc. and stock ownership of Guardant Health, Inc. S.D. declares honoraria from Novartis, Pfizer, Lilly, AstraZeneca, Roche, MSD, BMS, New Bridge, and Caris as well as research funding from MSD, Amgen, and the Al Jalila Foundation. N.R. declares employment from Fortis Memorial Research Institute; stock and other ownership interests from Datar Cancer Genetics; honoraria from Lilly, Roche India, and Guardant Health AMEA; a consulting or advisory role at Guardant Health AMEA; and travel, accommodations, expenses from Guardant Health AMEA. The other authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
a Characteristics of samples tested. ctDNA, circulating tumor DNA. b Cancer types profiled. BTC, billiary tract cancer; CCA, cholangiocarcinoma; GBC, gall bladder cancer; GEJ, gastro-esophageal junction.
Fig. 2.
Fig. 2.
Genomic landscape of gastrointestinal cancers. Genes most frequently affected by SNVs (a), amplifications (b), fusions (c), and fusion genes with partners (d). SNVs, single nucleotide variants.
Fig. 3.
Fig. 3.
Frequency of NCCN biomarkers in pancreatic adenocarcinoma. NCCN, National Comprehensive Cancer Network; MSI-H, microsatellite instability-high.
Fig. 4.
Fig. 4.
In-depth analysis of KRAS mutations in pancreatic adenocarcinoma, including the most frequent KRAS mutations (a) and location of KRAS mutations (b).
Fig. 5.
Fig. 5.
Frequency of NCCN biomarkers in colorectal cancer. NCCN, National Comprehensive Cancer Network; MSI-H, microsatellite instability-high.
Fig. 6.
Fig. 6.
KRAS/NRAS alterations in colorectal cancer. Most frequent KRAS mutations (a), most frequent NRAS mutations (b), and location of RAS mutations (c).
Fig. 7.
Fig. 7.
Ftequency of NCCN biomarkers in biliary tract cancers. NCCN, National Comprehensive Cancer Network; MSI-H, microsatellite instability-high.
Fig. 8.
Fig. 8.
Prevalence of NCCN biomarkers in gastric/GEJ adenocarcinomas. GEJ, gastro-esophageal junction; MSI-H, microsatellite instability-high.
Fig. 9.
Fig. 9.
Database analysis for pancreatic (a), colorectal (b), biliary tract (c), and gastric (d) cancers.
See this image and copyright information in PMC

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References

    1. Berger MF, Mardis ER. The emerging clinical relevance of genomics in cancer medicine. Nat Rev Clin Oncol. 2018;15(6):353–65. - PMC - PubMed
    1. Huo J, Xu Y, Sheu T, Volk RJ, Shih YC. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting. JAMA Intern Med. 2019;179(3):324–32. - PMC - PubMed
    1. Almendro V, Kim HJ, Cheng Y-K, Gönen M, Itzkovitz S, Argani P, et al. Genetic and phenotypic diversity in breast tumor metastases. Cancer Res. 2014;74(5):1338–48. - PMC - PubMed
    1. Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92. - PMC - PubMed
    1. Connal S, Cameron JM, Sala A, Brennan PM, Palmer DS, Palmer JD, et al. Liquid biopsies: the future of cancer early detection. J Transl Med. 2023;21(1):118. - PMC - PubMed