Clinico-pathological Study of K-ras Mutations in Colorectal Tumors in Saudi Arabia

Zahrani, Ali; Kandil, Magdy; Badar, Talha; Abdelsalam, Mahmoud; Al-Faiar, Abdulla; Ismail, Abdelsalam

doi:10.1177/1430.15819

Cited by 17 publications

(26 citation statements)

References 20 publications

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“…However, tumors harboring KRAS mutations constitute a heterogeneous group of colorectal cancers. KRAS mutation frequency has been reported to be 31.9-56% by different studies (10,(14)(15)(16)(17). The present study was performed to determine the association of KRAS mutation status with demographic and clinicopathological characteristics and anatomical location of the tumor.…”

Section: Discussionmentioning

confidence: 92%

Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors

Kodaz

Hacıbekiroğlu

Erdoğan

et al. 2014

Molecular and Clinical Oncology

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The aim of this study was to investigate the clinicopathological characteristics and distribution by tumor localization of KRAS point mutations in metastatic colorectal cancer. A total of 189 patients diagnosed with colorectal cancer between 2007 and 2014, who were either metastatic at the time of diagnosis or developed metastasis subsequently, were included in this study. KRAS mutation analysis was performed in the primary tumor tissues and KRAS mutations were identified in 47.6% of the patients. There was a high frequency of the p.G13D point mutation in left-colon tumors (P=0.011), while the p.G12D point mutation was more frequent in right-colon tumors (P=0.004). KRAS wild-type frequency (P=0.02) was higher among patients aged <40 years. A comparison of codon 12 and 13 mutations revealed that codon 12 mutations were more common in the >50-year-old group (P=0.03) and codon 13 mutations were more common in the <70-year-old group (P=0.04). KRAS wild-type tumors were localized in the right colon (P=0.005) and tumors with the p.G13D point mutation (P=0.018) were diagnosed at non-metastatic stages. In conclusion, KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization. In addition, the p.G13D point mutation was found to differ from other mutations in several aspects.

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Section: Discussionmentioning

confidence: 92%

Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors

Kodaz

Hacıbekiroğlu

Erdoğan

et al. 2014

Molecular and Clinical Oncology

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“…The frequency of KRAS mutations varies worldwide, ranging from 13% to 56% (Roth et al, 2010;Montomoli et al, 2012;Murtaza et al, 2014;Zahrani et al, 2014;Peeters et al, 2015). The frequency of KRAS mutations (47.2%) in the current study was consistent with the published data from Asian countries (Asaka et al, 2009;Lin et al, 2011;Ahn et al, 2014;Tong et al, 2014), Western countries (Lamy et al, 2011;Vaughn et al, 2011;Bozzao et al, 2012), and the TCGA database (Cancer Genome Atlas Network, 2012) -but not with all reports (Liou et al, 2011;Chaiyapan et al, 2013;Phipps et al, 2013;Rosty et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

Korphaisarn

Pongpaibul

Roothumnong

et al. 2019

Asian Pac J Cancer Prev

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Background: KRAS, NRAS, and BRAF gene mutations are the most clinically relevant and frequently reported in colorectal cancer (CRC). Although data on these genes are frequently reported in several counties, data specific to these genes among Thai population are scarce. The aim of this study was to investigate and identify molecular alterations associated with colon cancer in Thai population, and to determine the impact of these genetic aberrations on clinical outcome. Methods:DNA from 108 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma of stage II-III colon cancer between 2010 and 2012 at Siriraj Hospital (Bangkok, Thailand) were extracted. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Solid Tumor DNA kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Results:A total of 22 somatic gene mutations were detected. The mutation frequency observed in KRAS, NRAS, BRAF, PIK3CA, and FBXW7 mutations was 47.2%, 1.9%, 1.9%, 12%, and 14.8%, respectively. KRAS mutation codon 12, 13, 59, 61, 117, and 146 mutations were identified in 29.6%, 8.3%, 1.8%, 0.9%, 0.0%, and 8.3%, respectively. KRAS Exon 4 had better DFS compared with Exon 2 and 3. Conclusions:This study is the first to comprehensively report hotspot mutations using NGS in Thai colon cancer patients. The most commonly identified gene mutation frequencies among Thai patients (KRAS, NRAS, BRAF, TP53, and PIK3CA) were similar to the gene mutation frequencies reported in Western population, except for subgroup of KRAS codon 146 and FBXW7 mutations that had a slightly higher frequency.

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“…In our review, considering all stages, noticeably lower frequencies of mutation have been reported in Pakistan (13%) [19], Morocco (24%) [22] and one study from Saudi Arabia (28%) [14], while higher frequencies have been reported in other studies from Saudi Arabia (56% & 41%) [13,18], Turkey (33%, 44% & 45%) [12,15,17] and Jordan (44%) [20]. In Oman, a ME country in the Gulf region, the frequency of mutation in 100 patients with unreported stage was 31% [21].…”

Section: Geographic Differences In Kras Mutation Ratesmentioning

confidence: 47%

Frequency and Clinical Impact of KRAS Mutations in Patients with Colorectal Cancer from the Middle East

Zekri

Karim²,

Alshehri

et al. 2016

J. Anal. Oncol.

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Background: Colorectal cancer (CRC) is a significant healthcare burden worldwide and in the Middle East (ME). KRAS mutation confers resistance to epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced CRC. Data regarding the rate of KRAS mutation from the ME are scattered and scarce. We aim to collect and review all sizable studies evaluating the frequency of KRAS mutations in CRC patients from the ME. Method:A Pubmed and Google Scholar search was conducted using keywords including KRAS, K-ras, colorectal cancer and Middle East, along with names of each ME country. Studies including over 90 patients were included in the review.Result: Eleven studies containing more than 90 patients were identified. Among all eleven studies, KRAS mutation rate ranged from 13 to 56%. Five studies reported KRAS mutation rate in M1 stage either exclusively or as part of subgroup analysis. In these studies, mutations were found in 8-45% of cases. KRAS mutations were associated with female gender, M1 stage and high CEA in 3, 2, and 1 studies respectively. Conclusion:There is a broad range of variability in KRAS mutation rate reported in different studies from the ME. This may have been due to small number of patients in the studies and lack of centralized testing for KRAS mutations. Larger and more coordinated studies from the ME population are required to ascertain the accuracy of KRAS mutation rate.

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Clinico-pathological Study of K-ras Mutations in Colorectal Tumors in Saudi Arabia

Abstract: K-ras mutations are common among the Saudi colorectal cancer population, especially pG12V and pG12D in codon 12, and are more frequent in sigmoid and rectal adenocarcinomas and stage IVB tumors.

Cited by 17 publications

References 20 publications

Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors

Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

Frequency and Clinical Impact of KRAS Mutations in Patients with Colorectal Cancer from the Middle East

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