Mutational analyses of the BRAF, KRAS, and PIK3CA genes in oral squamous cell carcinoma.
OBJECTIVE
The development of oral squamous cell carcinoma (OSCC) is a complex, multistep process. To date, numerous oncogenes and tumor-suppressor genes have been implicated in oral carcinogenesis. Of particular interest in this regard are genes involved in cell cycling and apoptosis, such BRAF, KRAS, and PIK3CA genes.


METHODS
Mutations of BRAF, KRAS, and PIK3CA were evaluated by direct genomic sequencing of exons 1 of KRAS, 11 and 15 of BRAF, and 9 and 20 of PIK3CA in OSCC specimens.


RESULTS
Both BRAF and KRAS mutations were detected with a mutation frequency of 2% (1/42). PIK3CA mutations were detected at 3% (1/35).


CONCLUSIONS
This is the first report implicating BRAF mutation in OSCC. Our study supports that mutations in the BRAF, KRAS, and PIK3CA genes make at least a minor contribution to OSCC tumorigenesis, and pathway-specific therapies targeting these 2 pathways should be considered for OSCC in a subset of patients with these mutations.
Bruckman
Karl C
KC
College of Dental Medicine, Columbia University Medical Center, New York, NY, USA.
Schönleben
Frank
F
Qiu
Wanglong
W
Woo
Victoria L
VL
Su
Gloria H
GH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D005887:Gingival Neoplasms / Q000235:genetics; D006801:Humans; D008297:Male; D008339:Mandibular Neoplasms / Q000235:genetics; D008441:Maxillary Neoplasms / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D014062:Tongue Neoplasms / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Nature. 1993 Oct 28;365(6449):781-3
8413661
J Oral Pathol Med. 1990 Aug;19(7):301-5
2231435
Head Neck. 1999 Dec;21(8):751-9
10562689
Oral Oncol. 2000 Jan;36(1):76-80
10889924
Laryngoscope. 1994 Nov;104(11 Pt 1):1337-47
7968162
Int J Cancer. 1991 May 30;48(3):409-12
2040536
Genomics. 1994 Dec;24(3):472-7
7713498
Cancer Res. 2002 Dec 1;62(23):7001-3
12460919
Clin Cancer Res. 2003 Jun;9(6):2300-6
12796399
Mol Carcinog. 2006 Oct;45(10):721-31
16676365
Cancer Sci. 2006 Dec;97(12):1351-8
17052259
Int J Cancer. 2008 Mar 1;122(5):1189-94
17990317
Mol Cell Biol. 1997 Sep;17(9):5598-611
9271435
Cancer Res. 2002 Dec 15;62(24):7154-6
12499248
Oral Oncol. 2007 Jan;43(1):60-6
16807070
J Clin Endocrinol Metab. 2005 Aug;90(8):4688-93
15928251
Biochim Biophys Acta. 2003 Jun 5;1653(1):25-40
12781369
Oncogene. 2005 Feb 17;24(8):1477-80
15608678
Mol Pathol. 2000 Aug;53(4):165-72
11040937
Mamm Genome. 2005 Mar;16(3):211-7
15834638
Clin Cancer Res. 2005 Apr 15;11(8):2875-8
15837735
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):802-7
15647370
J Biol Chem. 1999 Mar 26;274(13):8347-50
10085060
Exp Cell Res. 1999 Nov 25;253(1):239-54
10579926
Cancer Metastasis Rev. 1994 Mar;13(1):67-89
8143346
Oral Oncol. 2007 Feb;43(2):107-15
17275742
Clin Cancer Res. 2006 Jun 15;12(12):3851-5
16778113
Clin Cancer Res. 2006 Mar 1;12(5):1441-6
16533766
Science. 2004 Apr 23;304(5670):554
15016963
Nature. 2002 Jun 27;417(6892):949-54
12068308
Br J Cancer. 1991 Apr;63(4):573-8
2021541
Surg Oncol. 1992 Dec;1(6):405-11
1341278
Trends Genet. 1994 Feb;10(2):44-8
8191584
Oncogene. 2003 Jul 24;22(30):4757-9
12879021
Cancer Res. 2004 Aug 1;64(15):5054-8
15289303
Eur J Cancer B Oral Oncol. 1996 May;32B(3):150-3
8762870
Cancer Lett. 2007 May 8;249(2):242-8
17097223
Int J Cancer. 2006 May 15;118(10):2644-6
16380997
Br J Cancer. 1990 Mar;61(3):365-8
2183872
Mol Cell Biol. 1996 Jul;16(7):3923-33
8668210
Cancer Res. 2002 Nov 15;62(22):6451-5
12438234
Arch Otolaryngol Head Neck Surg. 1994 Jul;120(7):755-60
7912510
Mayo Clin Proc. 2007 Jul;82(7):878-87
17605971
Annu Rev Biochem. 1987;56:779-827
3304147