Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer
ARMS-PCR
KRAS
NRAS
Sporadic colorectal cancer
real-time PCR
Tunisia
Journal
Turkish journal of medical sciences
ISSN: 1303-6165
Titre abrégé: Turk J Med Sci
Pays: Turkey
ID NLM: 9441758
Informations de publication
Date de publication:
26 02 2021
26 02 2021
Historique:
received:
05
03
2020
accepted:
31
08
2020
entrez:
7
9
2020
pubmed:
8
9
2020
medline:
26
10
2021
Statut:
epublish
Résumé
Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing rate of incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with antiepidermal growth factor receptor (EGFR) monoclonal antibodies. In this study, we aimed to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and explore their correlations with clinicopathological features. AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3, and 4) in 96 CRC tumors. KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12’s most abundant mutations were G12D and G12V, followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (P = 0.029), left-sided tumors (P = 0.037), and greater differentiation (P = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages of the disease (P = 0.039) and the absence of lymph node metastasis (P = 0.045). It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutations is crucial for the orientation of therapies and the selection of appropriate candidates, while also helping to avoid unnecessary toxicity and increased costs for patients.
Sections du résumé
Background/aim
Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing rate of incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with antiepidermal growth factor receptor (EGFR) monoclonal antibodies. In this study, we aimed to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and explore their correlations with clinicopathological features.
Materials and methods
AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3, and 4) in 96 CRC tumors.
Results
KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12’s most abundant mutations were G12D and G12V, followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (P = 0.029), left-sided tumors (P = 0.037), and greater differentiation (P = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages of the disease (P = 0.039) and the absence of lymph node metastasis (P = 0.045).
Conclusion
It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutations is crucial for the orientation of therapies and the selection of appropriate candidates, while also helping to avoid unnecessary toxicity and increased costs for patients.
Identifiants
pubmed: 32892548
doi: 10.3906/sag-2003-42
pmc: PMC7991861
doi:
Substances chimiques
Antibodies, Monoclonal
0
Codon
0
KRAS protein, human
0
Membrane Proteins
0
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
148-158Informations de copyright
This work is licensed under a Creative Commons Attribution 4.0 International License.
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interest.
Références
Indian J Cancer. 2014 Oct-Dec;51(4):531-7
pubmed: 26842186
BMJ Open. 2014 May 23;4(5):e004652
pubmed: 24859998
World J Gastroenterol. 2015 Feb 7;21(5):1595-605
pubmed: 25663779
Mol Biol Rep. 2013 Nov;40(11):6107-12
pubmed: 24078161
PLoS One. 2018 Jun 7;13(6):e0198795
pubmed: 29879227
Asian Pac J Cancer Prev. 2011;12(4):1073-6
pubmed: 21790254
Sci Rep. 2015 Dec 22;5:18678
pubmed: 26691448
Diagn Mol Pathol. 2010 Sep;19(3):157-63
pubmed: 20736745
Clin Colorectal Cancer. 2013 Sep;12(3):168-78
pubmed: 23773459
Lancet Oncol. 2010 Aug;11(8):753-62
pubmed: 20619739
N Engl J Med. 2008 Oct 23;359(17):1757-65
pubmed: 18946061
Heliyon. 2019 Mar 19;5(3):e01330
pubmed: 30949599
In Vivo. 2017 Jul-Aug;31(4):527-542
pubmed: 28652417
PLoS One. 2013;8(4):e60142
pubmed: 23573237
Oncol Lett. 2016 Jul;12(1):150-156
pubmed: 27347117
J Natl Compr Canc Netw. 2009 Sep;7(8):778-831
pubmed: 19755046
Intest Res. 2018 Jul;16(3):327-337
pubmed: 30090031
Cell Physiol Biochem. 2018;50(4):1496-1509
pubmed: 30359964
Mol Biol Rep. 2013 Jun;40(6):4109-14
pubmed: 23640097
Mol Cancer. 2014 May 31;13:135
pubmed: 24885062
J Oncol Pract. 2016 Feb;12(2):180-1
pubmed: 26443838
PLoS One. 2013;8(1):e54510
pubmed: 23355875
Cancer. 2014 May 15;120(10):1482-90
pubmed: 24500602
Cancer Biomark. 2013;13(2):89-97
pubmed: 23838137
Int J Cancer. 2006 Jun 1;118(11):2765-71
pubmed: 16381005
Cell. 1990 Jun 1;61(5):759-67
pubmed: 2188735
Pathol Res Pract. 2007;203(7):489-97
pubmed: 17629419
Invest Clin. 2009 Mar;50(1):55-63
pubmed: 19418727
J Clin Oncol. 2009 Apr 20;27(12):2091-6
pubmed: 19188670
PLoS One. 2013 Dec 10;8(12):e81628
pubmed: 24339949
Am J Surg. 2016 Sep;212(3):537-544.e3
pubmed: 27394063
Cell Biochem Biophys. 2012 Apr;62(3):415-20
pubmed: 22048888
Neoplasma. 2012;59(4):376-83
pubmed: 22489692
BMC Res Notes. 2017 Aug 10;10(1):392
pubmed: 28797274
N Engl J Med. 1988 Sep 1;319(9):525-32
pubmed: 2841597
Cancer Biomark. 2010-2011;8(6):331-40
pubmed: 22072121
PeerJ. 2018 Feb 05;6:e4341
pubmed: 29423347
Cancer Biol Ther. 2014 Jun 1;15(6):768-76
pubmed: 24642870
Asian Pac J Cancer Prev. ;18(10):2733-2739
pubmed: 29072401
Oncotarget. 2018 May 8;9(35):24081-24096
pubmed: 29844874
BMC Gastroenterol. 2019 Mar 27;19(1):46
pubmed: 30917791
CA Cancer J Clin. 2017 Mar;67(2):93-99
pubmed: 28094848
Mod Pathol. 2018 Mar;31(3):517-526
pubmed: 29052598
Oncol Lett. 2018 Jul;16(1):9-18
pubmed: 29928381
Tumour Biol. 2017 Feb;39(2):1010428317692265
pubmed: 28222664
Int J Oncol. 2005 Mar;26(3):745-50
pubmed: 15703832
Sci Rep. 2018 Apr 17;8(1):6076
pubmed: 29666387
Gastroenterology Res. 2018 Aug;11(4):264-273
pubmed: 30116425
Oncol Lett. 2018 Mar;15(3):3161-3166
pubmed: 29435051
Int J Cancer. 2015 Jan 1;136(1):83-90
pubmed: 24806288
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Pathol Res Pract. 2009;205(12):858-62
pubmed: 19679400
N Engl J Med. 2013 Sep 12;369(11):1023-34
pubmed: 24024839