Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications
Background: KRAS is one of the most frequently mutated oncogenes in humans. KRAS aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes. Objectives: We identified features of genetic alterations in KRAS , including single amino acid substituti...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-08-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359251351438 |
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| author | Jaeyun Jung Jung Yong Hong Se Hoon Park Joon Oh Park Young Suk Park Ho Yeong Lim Won Ki Kang Jeeyun Lee Sang Yun Ha Soomin Ahn Sung Hee Lim Seung Tae Kim |
| author_facet | Jaeyun Jung Jung Yong Hong Se Hoon Park Joon Oh Park Young Suk Park Ho Yeong Lim Won Ki Kang Jeeyun Lee Sang Yun Ha Soomin Ahn Sung Hee Lim Seung Tae Kim |
| author_sort | Jaeyun Jung |
| collection | DOAJ |
| description | Background: KRAS is one of the most frequently mutated oncogenes in humans. KRAS aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes. Objectives: We identified features of genetic alterations in KRAS , including single amino acid substitutions and amplifications, based on the results of next-generation sequencing tests in 1667 advanced solid tumor patients. Design: Retrospective cohort study. Methods: Among 1667 patients, 28.1% ( N = 468) had KRAS aberrations (single-nucleotide variant (SNV): N = 438, 26.1%; amplification (copy number variation): N = 48, 2.9%) in metastatic solid tumors. Results: The incidence rate of SNVs was higher in pancreatic cancer ( N = 89, 89.9%) than in other tumors, including colorectal cancer ( N = 259, 47.3%) and small bowel cancer ( N = 4, 40.0%). Most of the mutations were missense mutations ( N = 434, 99.1%). In addition, we examined the specific location of SNVs; the mutational type G12D ( N = 178, 40.6%) was the most frequent, followed by G12V ( N = 95, 21.7%) and G13D ( N = 47, 10.7%). In the survival analysis, the mutational types of G12V and G13D influenced the poor survival of patients (G12V, the mutant type; 245 vs the wild type; 531 days; G13D, the mutant type; 435 vs the wild type; 531 days). Conclusion: In patients with KRAS amplification, the copy number range varied among the tumor types. Bladder cancer (147.9), cholangiocarcinoma (16.2), and gastric cancer (11.0) had relatively high median copy numbers of KRAS . Overall, our data are expected to provide valuable information for patients with various metastatic solid tumors and KRAS aberrations. |
| format | Article |
| id | doaj-art-ae2ba6cb31124aab8bdee9c9b08a56b6 |
| institution | DOAJ |
| issn | 1758-8359 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj-art-ae2ba6cb31124aab8bdee9c9b08a56b62025-08-20T03:06:16ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592025-08-011710.1177/17588359251351438Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implicationsJaeyun JungJung Yong HongSe Hoon ParkJoon Oh ParkYoung Suk ParkHo Yeong LimWon Ki KangJeeyun LeeSang Yun HaSoomin AhnSung Hee LimSeung Tae KimBackground: KRAS is one of the most frequently mutated oncogenes in humans. KRAS aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes. Objectives: We identified features of genetic alterations in KRAS , including single amino acid substitutions and amplifications, based on the results of next-generation sequencing tests in 1667 advanced solid tumor patients. Design: Retrospective cohort study. Methods: Among 1667 patients, 28.1% ( N = 468) had KRAS aberrations (single-nucleotide variant (SNV): N = 438, 26.1%; amplification (copy number variation): N = 48, 2.9%) in metastatic solid tumors. Results: The incidence rate of SNVs was higher in pancreatic cancer ( N = 89, 89.9%) than in other tumors, including colorectal cancer ( N = 259, 47.3%) and small bowel cancer ( N = 4, 40.0%). Most of the mutations were missense mutations ( N = 434, 99.1%). In addition, we examined the specific location of SNVs; the mutational type G12D ( N = 178, 40.6%) was the most frequent, followed by G12V ( N = 95, 21.7%) and G13D ( N = 47, 10.7%). In the survival analysis, the mutational types of G12V and G13D influenced the poor survival of patients (G12V, the mutant type; 245 vs the wild type; 531 days; G13D, the mutant type; 435 vs the wild type; 531 days). Conclusion: In patients with KRAS amplification, the copy number range varied among the tumor types. Bladder cancer (147.9), cholangiocarcinoma (16.2), and gastric cancer (11.0) had relatively high median copy numbers of KRAS . Overall, our data are expected to provide valuable information for patients with various metastatic solid tumors and KRAS aberrations.https://doi.org/10.1177/17588359251351438 |
| spellingShingle | Jaeyun Jung Jung Yong Hong Se Hoon Park Joon Oh Park Young Suk Park Ho Yeong Lim Won Ki Kang Jeeyun Lee Sang Yun Ha Soomin Ahn Sung Hee Lim Seung Tae Kim Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications Therapeutic Advances in Medical Oncology |
| title | Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications |
| title_full | Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications |
| title_fullStr | Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications |
| title_full_unstemmed | Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications |
| title_short | Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications |
| title_sort | comprehensive analysis of aberrations in pan cancer with a focus on prognostic and therapeutic implications |
| url | https://doi.org/10.1177/17588359251351438 |
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