Clinicopathological, molecular, and prognostic features of colorectal carcinomas with <scp><i>KRAS</i></scp> c.<scp>34G</scp>>T (p.<scp>G12C</scp>) mutation-Reference-Cited by-同舟云学术

Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation

Published:2024-07-22 Issue: Volume: Page:
ISSN:1347-9032
Container-title:Cancer Science
language:en
Short-container-title:Cancer Science

Author:

Ugai Satoko¹²,Yao Qian¹,Takashima Yasutoshi¹³,Zhong Yuxue¹,Matsuda Kosuke¹,Kawamura Hidetaka¹⁴,Imamura Yu⁵^ORCID,Okadome Kazuo¹,Mima Kosuke⁶,Arima Kota⁶,Kosumi Keisuke⁶,Song Mingyang²⁷⁸⁹,Meyerhardt Jeffrey A.³,Giannakis Marios³¹⁰¹¹,Nowak Jonathan A.¹³,Ugai Tomotaka¹²^ORCID,Ogino Shuji¹²¹⁰¹²¹³

Affiliation:

1. Program in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital, and Harvard Medical School Boston Massachusetts USA

2. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA

3. Department of Medical Oncology Dana‐Farber Cancer Institute and Harvard Medical Boston Massachusetts USA

4. Department of Surgery Fukushima Medical University Fukushima Japan

5. Department of Esophageal Surgery The Cancer Institute Hospital of the Japanese Foundation of Cancer Research Tokyo Japan

6. Department of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan

7. Department of Nutrition Harvard T.H. Chan School of Public Health Boston Massachusetts USA

8. Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

9. Division of Gastroenterology Massachusetts General Hospital Boston Massachusetts USA

10. Broad Institute of MIT and Harvard Cambridge Massachusetts USA

11. Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA

12. Cancer Immunology Program Dana‐Farber/Harvard Cancer Center Boston Massachusetts USA

13. Tokyo Medical and Dental University (Institute of Science Tokyo) Tokyo Japan

Abstract

AbstractEvidence indicates that combinations of anti‐EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)‐low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS‐wild‐type tumors (31%). KRAS c.34G>T mutants showed higher CIMP‐high prevalence (14%) and lower CIMP‐negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T‐mutated tumors were associated with cecal location, non‐microsatellite instability (MSI)‐high status, BRAF wild type, and PIK3CA mutation when compared with KRAS‐wild‐type tumors. Compared with BRAF‐mutated tumors, KRAS c.34G>T mutants showed more frequent LINE‐1 hypomethylation, a biomarker for early‐onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+ Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF‐wild‐type colorectal carcinomas, compared with KRAS‐wild‐type tumors, multivariable‐adjusted colorectal cancer‐specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05–3.17) in KRAS c.34G>T (p.G12C)‐mutated tumors (p = 0.035) and 1.57 (1.22–2.02) in other KRAS‐mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma.

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.16262

Reference56 articles.

1. General insight into cancer: An overview of colorectal cancer (Review)

2. The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer

3. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer

4. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer

5. K-rasMutations and Benefit from Cetuximab in Advanced Colorectal Cancer