TP53 mutations in colorectal cancer from Tunisia: relationships with site of tumor origin, microsatellite instability and KRAS mutations
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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.
KeywordsCRC TP53 KRAS MSI
Familial adenomatous polyposis
Hereditary nonpolyposis colorectal cancer
Multiplex ligation dependent probe amplification
Tumor protein 53
This study was the result of collaboration between the Universities of Tunis-El Manar and Lille 2. S.A was supported in part by a grant from the Tunisian government. We are indebted to all family members who agreed to attend our study. We also thank Dr O. Trabelsi, Gastroenterologist in Tunis, Tunisia, for providing us with families, Dr A. Wacrenier, Department of Pathology of the CHRU of Lille, France, for her help in immunohistochemistry of MMR and TP53 proteins, and the “Plateau Commun de Biologie Moléculaire du Centre de Biologie-Pathologie” of the CHRU of Lille.
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