P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations.
CRC-associated P53 mutations have not been studied extensively in non-Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin-embedded CRC cases from Northern Iran for mutations in P53 exons 5-8 using PCR-direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability (MSI-H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI-H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non-mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K-ras transversions. Transitions at non-CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K-ras transitions and MSI-H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI-H were as reported for non-Iranian patients. However P53 mutation site/type and correlations between P53 and K-ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran.
Mahdavinia
Mahboobeh
M
Department of Oncology and Neurosciences, University G. d'Annunzio, and Center of Excellence on Aging (CeSI), G. d'Annunzio University Foundation, Chieti, Italy.
Bishehsari
Faraz
F
Verginelli
Fabio
F
Cumashi
Albana
A
Lattanzio
Rossano
R
Sotoudeh
Masoud
M
Ansari
Reza
R
Semeraro
Daniela
D
Hormazdi
Mahshid
M
Fakheri
Hafez
H
Rakhshani
Naser
N
De Lellis
Laura
L
Curia
Maria Cristina
MC
Cama
Alessandro
A
Piantelli
Mauro
M
Malekzadeh
Reza
R
Iacobelli
Stefano
S
Mariani-Costantini
Renato
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53