TP53 mutations in colorectal cancer from Tunisia: relationships with site of tumor origin, microsatellite instability and KRAS mutations.
Loss of TP53 function through gene mutation is a critical event in the development and progression of colorectal cancer (CRC). Here we examined 51 primary CRC tumors from Tunisia for mutations in TP53 exons 4-9 using PCR-direct sequencing. TP53 status and mutation site/type were than correlated with nuclear protein accumulation, familial and clinicopathologic variables and data on KRAS mutations and microsatellite instability (MSI-H). The TP53 mutation analysis was possible in the tumor of 47 patients and a deleterious somatic mutation has been detected in 59.6% of the patients (28/47) including 20 (71.4%) missense mutations, 7 nonsense mutations (25%) and 1 (3.6%) frameshift mutation. 89.3% (25/28) of the detected mutations were in exons 5-8, whereas 10.7% (3/28) were in exon 4. Among the 27 non frameshift mutations, 89% (24/27) were transitions and 11% (3/27) were transversions. 64.3% (18/27) of the altered amino acids corresponded to arginine. 74% (20/27) were G>C to A>T transitions, and more than half (14/27) occur at hotspots codons with CpG sites. TP53 mutations correlated closely with TP53 accumulation (p = 0.0090) and inversely with MSI phenotype (p = 0.0658). A KRAS somatic mutation was identified in 25% (7/28) of the TP53 mutated tumors. All these mutations were G>A transitions in codon 12 and all the tumors with combined alterations but one were distally located and MSS. In conclusion, frequency and types of TP53 mutations and correlations with TP53 protein accumulation, and MSI were as reported for non-Tunisian patients. However, no significant associations have been detected between TP53 mutations and clinicopathological data in Tunisian patients as previously reported.
Laboratory of Biochemistry and Molecular Biology, Science University of Tunis, Tunis, Tunisia, sana.aissi@hotmail.com.
Sana
S
Aissi
Marie-Pierre
MP
Buisine
Farid
F
Zerimech
Nadia
N
Kourda
Amel
A
Moussa
Mohamed
M
Manai
Nicole
N
Porchet
D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014416:Tunisia; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins