Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer: Huan Peng, Jun Ying, Jia Zang, Hao Lu, Xiaokai Zhao, Pengmin Yang, Xintao Wang, Jieyi Li, Ziying Gong, Daoyun Zhang, Zhiguo Wang; Cancer Res Treat. 2023;55(4):1270-1280. Published online April 24, 2023; DOI: https://doi.org/10.4143/crt.2023.415

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Purpose
Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC.
Materials and Methods
Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed.
Results
APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations.
Conclusion
APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

Citations

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In Silico Validation of OncoOrigin: An Integrative AI Tool for Primary Cancer Site Prediction with Graphical User Interface to Facilitate Clinical Application
Petar Brlek, Luka Bulić, Nidhi Shah, Parth Shah, Dragan Primorac
International Journal of Molecular Sciences.2025; 26(6): 2568. CrossRef
Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation
Muhammad Tufail, Can-Hua Jiang, Ning Li
Molecular Cancer.2025;[Epub] CrossRef
Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies
Neelakanta Sarvashiva Kiran, Chandrashekar Yashaswini, Rahul Maheshwari, Sankha Bhattacharya, Bhupendra G. Prajapati
ACS Pharmacology & Translational Science.2024; 7(4): 967. CrossRef
Clinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients
Qingqing Qiu
American Journal of Cancer Research.2024; 14(2): 796. CrossRef
Mechanism of APC truncation involved in colorectal cancer tumorigenesis (Review)
Tuya Wang, Jing Fu, Ye Huang, Chun Fu
Oncology Letters.2024;[Epub] CrossRef

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Breast cancer

Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation: Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park; Cancer Res Treat. 2023;55(1):155-166. Published online June 8, 2022; DOI: https://doi.org/10.4143/crt.2021.1567

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Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

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Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
Journal of Personalized Medicine.2023; 13(5): 866. CrossRef

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