Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients
Abstract Background The incidence of colorectal cancer (CRC) in young adults has increased worldwide. Our study aimed to evaluate genomic alterations in early-onset (aged 15–39 years) sporadic CRC. Methods Formalin-fixed, paraffin-embedded tissue samples from 90 patients with histologically confirme...
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BMC
2025-02-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13745-5 |
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| author | Ben Ponvilawan Phuwanat Sakornsakolpat Ananya Pongpaibul Ekkapong Roothumnong Charuwan Akewanlop Manop Pithukpakorn Krittiya Korphaisarn |
| author_facet | Ben Ponvilawan Phuwanat Sakornsakolpat Ananya Pongpaibul Ekkapong Roothumnong Charuwan Akewanlop Manop Pithukpakorn Krittiya Korphaisarn |
| author_sort | Ben Ponvilawan |
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| description | Abstract Background The incidence of colorectal cancer (CRC) in young adults has increased worldwide. Our study aimed to evaluate genomic alterations in early-onset (aged 15–39 years) sporadic CRC. Methods Formalin-fixed, paraffin-embedded tissue samples from 90 patients with histologically confirmed colorectal adenocarcinoma with proficient mismatch repair status from Siriraj Hospital (Bangkok, Thailand) were extracted. Patients with clinically suspected familial adenomatous polyposis were excluded. A 517-gene mutational analysis was performed by next-generation sequencing using the Oncomine Comprehensive Assay Plus kit. The previously reported molecular data in adult-onset CRC from our group were used as a comparator group. Results The five most frequently mutated genes were APC (66%), TP53 (51%), KRAS (47%), ARID1A (31%), and KMT2B (31%). When compare with adult-onset, NOTCH1 (11.1% vs. 1.9%), FBXW7 (23.3% vs. 14.8%), PIK3CA (20% vs. 12.1%), and FGFR3 (8.9% vs. 3.7%) mutations were more prevalent in early-onset. No differences were observed in other common mutations, such as TP53, EGFR, KRAS, NRAS and BRAF mutations. An increased prevalence in KRAS codon 12 mutations was also observed in early-onset patients compared to the adult-onset group (38.9% vs. 29.6%). Conclusions Overall, the genomic landscape between early- and adult-onset CRC appears similar. However, our study revealed the enrichment of NOTCH1, FBXW7, PIK3CA, and FGFR3 along with KRAS G12 mutations, were more frequent in early-onset compared to adult-onset cases. Further studies with a larger cohort of patients on the comprehensive analysis of genetic/epigenetic signatures are required. |
| format | Article |
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| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-1728b39c57f4417bbbc2bccfbcb3dc082025-08-20T02:59:32ZengBMCBMC Cancer1471-24072025-02-012511710.1186/s12885-025-13745-5Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patientsBen Ponvilawan0Phuwanat Sakornsakolpat1Ananya Pongpaibul2Ekkapong Roothumnong3Charuwan Akewanlop4Manop Pithukpakorn5Krittiya Korphaisarn6Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityAbstract Background The incidence of colorectal cancer (CRC) in young adults has increased worldwide. Our study aimed to evaluate genomic alterations in early-onset (aged 15–39 years) sporadic CRC. Methods Formalin-fixed, paraffin-embedded tissue samples from 90 patients with histologically confirmed colorectal adenocarcinoma with proficient mismatch repair status from Siriraj Hospital (Bangkok, Thailand) were extracted. Patients with clinically suspected familial adenomatous polyposis were excluded. A 517-gene mutational analysis was performed by next-generation sequencing using the Oncomine Comprehensive Assay Plus kit. The previously reported molecular data in adult-onset CRC from our group were used as a comparator group. Results The five most frequently mutated genes were APC (66%), TP53 (51%), KRAS (47%), ARID1A (31%), and KMT2B (31%). When compare with adult-onset, NOTCH1 (11.1% vs. 1.9%), FBXW7 (23.3% vs. 14.8%), PIK3CA (20% vs. 12.1%), and FGFR3 (8.9% vs. 3.7%) mutations were more prevalent in early-onset. No differences were observed in other common mutations, such as TP53, EGFR, KRAS, NRAS and BRAF mutations. An increased prevalence in KRAS codon 12 mutations was also observed in early-onset patients compared to the adult-onset group (38.9% vs. 29.6%). Conclusions Overall, the genomic landscape between early- and adult-onset CRC appears similar. However, our study revealed the enrichment of NOTCH1, FBXW7, PIK3CA, and FGFR3 along with KRAS G12 mutations, were more frequent in early-onset compared to adult-onset cases. Further studies with a larger cohort of patients on the comprehensive analysis of genetic/epigenetic signatures are required.https://doi.org/10.1186/s12885-025-13745-5Genomic alterationsMolecular characteristicEarly onsetAdolescent and young adultColorectal cancer |
| spellingShingle | Ben Ponvilawan Phuwanat Sakornsakolpat Ananya Pongpaibul Ekkapong Roothumnong Charuwan Akewanlop Manop Pithukpakorn Krittiya Korphaisarn Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients BMC Cancer Genomic alterations Molecular characteristic Early onset Adolescent and young adult Colorectal cancer |
| title | Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients |
| title_full | Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients |
| title_fullStr | Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients |
| title_full_unstemmed | Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients |
| title_short | Comprehensive genomic analysis in sporadic early-onset colorectal adenocarcinoma patients |
| title_sort | comprehensive genomic analysis in sporadic early onset colorectal adenocarcinoma patients |
| topic | Genomic alterations Molecular characteristic Early onset Adolescent and young adult Colorectal cancer |
| url | https://doi.org/10.1186/s12885-025-13745-5 |
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