KRAS mutations and subtyping in colorectal cancer in Jordanian patients

Elbjeirami,Wafa   M.; Sughayer,Maher  A.

doi:10.3892/ol.2012.785

KRAS mutations and subtyping in colorectal cancer in Jordanian patients

Authors:
- Wafa M. Elbjeirami
- Maher A. Sughayer
View Affiliations

Affiliations: Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman 11941, Jordan
Published online on: July 4, 2012 https://doi.org/10.3892/ol.2012.785
Pages: 705-710

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and Jordan. v-Ki-ras2 Kirsten rat sarcoma (KRAS) mutations represent an early event in the development and progression of CRC. Previous studies have demonstrated that KRAS mutations serve as a predictor of response to EGFR‑targeted therapies for patients with metastatic CRC. The aim of this study was to determine the portion of CRC patients with wild‑type KRAS status and molecular subtypes of KRAS mutations in Jordan as compared with other countries. DNA was isolated from 100 consecutive colorectal carcinoma specimens from patients who underwent surgical resection or colonoscopic biopsies of colorectal tumors and had developed metastatic disease. KRAS mutations were detected by hybridization-based strip assay as well as RT‑PCR‑based assay and confirmed by standard Sanger sequencing of codon 12 and 13 of exon 1 of the KRAS gene. Among 100 tested patients, 56% had a wt-KRAS genotype and 44% had a mutated KRAS genotype. The pGly12Asp was the most commonly detected mutation (54.5%). KRAS mutations were independently associated with patient age, gender and tumoral variables. The ratio of mutated versus wt-KRAS patients in this study is similar to those reported in Western countries but contrasts to neighboring Middle Eastern countries. Colorectal carcinoma cases from Jordan had higher KRAS mutation frequencies compared with other Middle Eastern countries which is likely to reflect different molecular pathogenesis and environmental exposures.

View Figures

View References

1.	A JemalR SiegelE WardY HaoJ XuT MurrayMJ ThunCancer statistics, 2008CA Cancer J Clin587196200810.3322/CA.2007.0010
2.	M TarawnehO NimriK ArkoobM Al ZhagalCancer Incidence in Jordan annual report, 2009
3.	C PennaB NordlingerColorectal metastasis (liver and lung)Surg Clin North Am8210751090200210.1016/S0039-6109(02)00051-812507210
4.	JH Van KriekenA JungT KirchnerKRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance programVirchows Arch453417431200818802721
5.	K FransėnM KlintenäsA OsterströmMutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomasCarcinogenesis25527533200414688025
6.	DJ JonkerCJ O’CallaghanCS KarapetisCetuximab for the treatment of colorectal cancerN Engl J Med35720402048200710.1056/NEJMoa07183418003960
7.	E Van CutsemS SienaY HumbletAn open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapyAnn Oncol199298200817785764
8.	RG AmadoM WolfM PeetersE Van CutsemWild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancerJ Clin Oncol2616261634200810.1200/JCO.2007.14.711618316791
9.	S Khambata-FordCR GarrettNJ MeropolExpression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximabJ Clin Oncol2532303237200710.1200/JCO.2006.10.543717664471
10.	CS KarapetisS Khambata-FordDJ JonkerK-ras mutations and benefit from cetuximab in advanced colorectal cancerN Engl J Med35917571765200810.1056/NEJMoa080438518946061
11.	M ZenkerK LehmannAL SchulzExpansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutationsJ Med Genet44131135200710.1136/jmg.2006.04630017056636
12.	R WongD CunninghamUsing predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodiesJ Clin Oncol2656685670200810.1200/JCO.2008.19.502419001346
13.	T MinamotoM MaiZ RonaiK-ras mutation: early detection in molecular diagnosis and risk assessment of colorectal, pancreas, and lung cancers - a reviewCancer Detect Prev24112200010757118
14.	D CalistriC RengucciI SeymourMutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progressionJ Cell Physiol204484488200510.1002/jcp.2031015702478
15.	A LièvreJB BachetD Le CorreKRAS mutation status is predictive of response to cetuximab therapy in colorectal cancerCancer Res6639923995200616618717
16.	S EdkinsS O’MearaA ParkerRecurrent KRAS codon 146 mutations in human colorectal cancerCancer Biol Ther5928932200610.4161/cbt.5.8.325116969076
17.	P CejasM López-GómezC AguayoKRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasisPLoS One4e8199200910.1371/journal.pone.000819920020061
18.	CG FerreiraI Zalcberg-RenaultFM VieiraMH BonaminoM ZalisAnalysis of KRAS mutations in colorectal cancer (CRC) patients by gender in a Brazilian cohort of 3,346 patientsJ Clin Oncol2815s2010
19.	J AbubakerP BaviW Al-HaqawiPrognostic significance of alterations in KRAS isoforms KRAS-4A/4B and KRAS mutations in colorectal carcinomaJ Pathol219435445200910.1002/path.262519824059
20.	M ConzelmannU LinnemannMR BergerK-ras codon 12 and 13 mutations are correlated with differential patterns of tumor cell dissemination in colorectal cancer patientsInt J Oncol2415371544200415138598
21.	A LicarP CerkovnikJ OcvirkS NovakovicKRAS mutations in Slovene patients with colorectal cancer: frequency, distribution and correlation with the response to treatmentInt J Oncol3611371144201020372787
22.	ER FearonMolecular genetic studies of the adenoma-carcinoma sequenceAdv Intern Med3912314719948140953
23.	P ShawS TardyE BenitoOccurrence of Ki-ras and p53 mutations in primary colorectal tumorsOncogene62121212819911945416
24.	M Herreros-VillanuevaG AggarwalKRAS assay selection: sensitivity and accuracy in clinical applicationMol Biol Rep3924672470201210.1007/s11033-011-0997-621656377
25.	P PintoP RochaI VeigaComparison of methodologies for KRAS mutation detection in metastatic colorectal cancerCancer Genet20443946201110.1016/j.cancergen.2011.07.00321962894
26.	AS SolimanML BondySA El-BadawyContrasting molecular pathology of colorectal carcinoma in Egyptian and Western patientsBr J Cancer8510371046200110.1054/bjoc.2001.183811592777
27.	T NagasakaH SasamotoK NotoharaColorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylationJ Clin Oncol2245844594200410.1200/JCO.2004.02.15415542810
28.	N SharmaM SaifoI TamaskarR BhuvaneswariT MashtareM FakihKRAS status and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFOX chemotherapyJ Gastrointest Oncol19096201022811812
29.	HJ AndreyevAR NormanD CunninghamKirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ studyBr J Cancer856926962001
30.	D SantiniF LoupakisB VincenziHigh concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practiceOncologist1312701275200810.1634/theoncologist.2008-018119056857
31.	MC Etienne-GrimaldiJL FormentoM FrancoualK-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapyClin Cancer Res1448304835200810.1158/1078-0432.CCR-07-4906
32.	S ArtaleA Sartore-BianchiSM VeroneseMutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancerJ Clin Oncol2642174219200810.1200/JCO.2008.18.728618757341
33.	B VogelsteinER FearonSR HamiltonGenetic alterations during colorectal-tumor developmentN Engl J Med319525532198810.1056/NEJM1988090131909012841597