Mutational profile of KRAS, NRAS, BRAF, PIK3CA, and AKT1 genes in colorectal cancer patients in a tertiary care hospital, Dhaka

被引:1
作者
Chowdhury, Sharmin [1 ]
Ara, Sheikh Joly Ferdous [1 ]
Mili, Shirazum Monira [1 ]
Momotaz, Tahani [1 ]
Molla, Md Maruf Ahmed [2 ]
Anwar, Shaheda [1 ]
Abu Saleh, Ahmed [1 ]
机构
[1] Bangabandhu Sheikh Mujib Med Univ, Dept Microbiol & Immunol, Dhaka, Bangladesh
[2] Natl Inst Lab Med & Referral Ctr, Dept Virol, Dhaka, Bangladesh
来源
ADVANCES IN CANCER BIOLOGY-METASTASIS | 2022年 / 5卷
基金
英国医学研究理事会;
关键词
CRC; KRAS; NRAS; BRAF; PIK3CA; AKT1; Monoclonal antibody; Gene mutation; K-RAS GENE; PREVALENCE; RESISTANCE; FREQUENCY; THERAPY; ADENOCARCINOMAS; ASSOCIATION; PATHWAY; MARKERS; IMPACT;
D O I
10.1016/j.adcanc.2022.100054
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Colorectal carcinoma (CRC) is the third most common cancer in the world and incidences are on the rise in Bangladesh. KRAS, NRAS, BRAF, PIK3CA, and AKTI gene mutations are predictive markers of biological therapies, monoclonal antibodies targeting EGFR. The purpose of this study was to detect KRAS, NRAS, BRAF, PIK3CA, and AKT1 genes mutation in CRC patients by multiplex real-time Polymerase Chain Reaction (PCR) and evaluate the association of the mutations with clinicopathological features.Methodology: This cross-sectional study was carried out in the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2019 to January 2020. Tissues from surgically resected colorectal tumors were collected from 44 histopathologically confirmed adult colorectal cancer patients, who were admitted in the Department of Colorectal Surgery, BSMMU.Results: Among 44 histopathologically diagnosed colorectal cancer patients, KRAS, BRAF, and PIK3CA gene mutations were identified in 31.5%, 4.85%, and 4.85% tumors, respectively. In this study, no mutation was detected in NRAS and AKT1 genes. Concurrent mutation in KRAS and PIK3CA genes were found in one patient. Among the 14 KRAS mutant cases, most (92.85%) were in exon 2 (codon 12/13) and only 7.15% of the mutations were in exon 3 (codon 61). No mutation was detected in codon 59, 117, and 146. Among the two PIK3CA mutations, one was present in exon 9 and another was in exon 20. KRAS mutations were significantly associated with well and moderately differentiated tumors than poorly differentiated tumors (p < 0.05). Histopathologically there was no significant association of KRAS mutations with age, sex, tumor location, TNM staging, and other parameters.Conclusion: A combined evaluation of genetic biomarkers can classify about one-third of colorectal cancer patients as mutant for any one of these KRAS, BRAF, and PIK3CA genes.
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页数:6
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[41]   AKT1 and PIK3CA activating mutations in Moroccan bladder cancer patients' biopsies and matched urine [J].
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Arrouchi, Housna ;
Alaoui, Chaimae Hafidi ;
Tetou, Mohammed ;
Bensaid, Mounia ;
Oukabli, Mohamed ;
Ameur, Ahmed ;
Al Bouzidi, Abderrahmane ;
El Mzibri, Mohammed ;
Attaleb, Mohammed .
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[42]   Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing-based cohort study [J].
Jauhri, Mayank ;
Bhatnagar, Akanksha ;
Gupta, Satish ;
Bp, Manasa ;
Minhas, Sachin ;
Shokeen, Yogender ;
Aggarwal, Shyam .
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[43]   Genomic Profiling of KRAS/NRAS/BRAF/PIK3CA Wild-Type Metastatic Colorectal Cancer Patients Reveals Novel Mutations in Genes Potentially Associated with Resistance to Anti-EGFR Agents [J].
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Lambiase, Matilde ;
Fenizia, Francesca ;
Roma, Cristin ;
Cardone, Claudia ;
Iannaccone, Alessia ;
De Luca, Antonella ;
Carotenuto, Marianeve ;
Frezzetti, Daniela ;
Martinelli, Erika ;
Maiello, Evaristo ;
Ciardiello, Fortunato ;
Normanno, Nicola .
CANCERS, 2019, 11 (06)
[44]   The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis [J].
Therkildsen, Christina ;
Bergmann, Troels K. ;
Henrichsen-Schnack, Tine ;
Ladelund, Steen ;
Nilbert, Mef .
ACTA ONCOLOGICA, 2014, 53 (07) :852-864
[45]   Characteristics and prevalence of KRAS, BRAF, and PIK3CA mutations in colorectal cancer by high-resolution melting analysis in Taiwanese population [J].
Hsieh, Li-Ling ;
Er, Tze-Kiong ;
Chen, Chih-Chieh ;
Hsieh, Jan-Sing ;
Chang, Jan-Gowth ;
Liu, Ta-Chih .
CLINICA CHIMICA ACTA, 2012, 413 (19-20) :1605-1611
[46]   The Prevalence of BRAF, PIK3CA, and RAS Mutations in Indian Patients with Colorectal Cancer [J].
Shetty, Omshree ;
Vengurlekar, Vaibhavi ;
Kapoor, Akhil ;
Kamble, Vishakha ;
Gurav, Mamta ;
Bhargava, Prabhat ;
Srinivas, Sujay ;
Ramaswamy, Anant ;
Ramadwar, Mukta ;
Saklani, Avanish P. ;
Desouza, Ashwin ;
Ostwal, Vikas .
SOUTH ASIAN JOURNAL OF CANCER, 2022, 11 (03) :190-194
[47]   Mutational profiles of different macroscopic subtypes of colorectal adenoma reveal distinct pathogenetic roles for KRAS, BRAF and PIK3CA [J].
Li-Chun Chang ;
Han-Mo Chiu ;
Chia-Tung Shun ;
Jin-Tung Liang ;
Jaw-Town Lin ;
Chien-Chuan Chen ;
Yi-Chia Lee ;
Ming-Shiang Wu .
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[48]   Mutational Analysis of AKT1 and PIK3CA in Intraductal Papillomas of the Breast with Special Reference to Cellular Components [J].
Mishima, Chieko ;
Kagara, Naofumi ;
Ikeda, Jun-ichiro ;
Morii, Eiichi ;
Miyake, Tomohiro ;
Tanei, Tomonori ;
Naoi, Yasuto ;
Shimoda, Masafumi ;
Shimazu, Kenzo ;
Kim, Seung Jin ;
Noguchi, Shinzaburo .
AMERICAN JOURNAL OF PATHOLOGY, 2018, 188 (05) :1106-1112
[49]   The potential of PIK3CA, KRAS, BRAF, and APC hotspot mutations as a non-invasive detection method for colorectal cancer [J].
Alizadeh-Sedigh, Maryam ;
Mahmoodzadeh, Habibollah ;
Fazeli, Mohammad Sadegh ;
Haddadi-Aghdam, Mohammad ;
Teimoori-Toolabi, Ladan .
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[50]   Effectors of Epidermal Growth Factor Receptor Pathway: The Genetic Profiling of KRAS, BRAF, PIK3CA, NRAS Mutations in Colorectal Cancer Characteristics and Personalized Medicine [J].
Shen, Yinchen ;
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Han, Xiaohong ;
Yang, Hongying ;
Wang, Shuai ;
Lin, Dongmei ;
Shi, Yuankai .
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