Mahdavinia Mahboobeh, Bishehsari Faraz, Verginelli Fabio, Cumashi Albana, Lattanzio Rossano, Sotoudeh Masoud, Ansari Reza, Semeraro Daniela, Hormazdi Mahshid, Fakheri Hafez, Rakhshani Naser, De Lellis Laura, Curia Maria Cristina, Cama Alessandro, Piantelli Mauro, Malekzadeh Reza, Iacobelli Stefano, Mariani-Costantini Renato
Department of Oncology and Neurosciences, University G. d'Annunzio, and Center of Excellence on Aging (CeSI), G. d'Annunzio University Foundation, Chieti, Italy.
J Cell Physiol. 2008 Aug;216(2):543-50. doi: 10.1002/jcp.21428.
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.
在结直肠癌（CRC）风险相对较低的非西方国家，与CRC相关的P53突变尚未得到广泛研究。我们首次使用PCR直接测序法检测了来自伊朗北部的196例石蜡包埋的CRC病例中P53基因外显子5 - 8的突变情况。P53状态和突变位点/类型与核蛋白积累、临床病理变量以及K-ras突变和高微卫星不稳定性（MSI-H）数据相关。我们在87例（44.4%）病例中检测到96个P53突变，84例（42.8%）有蛋白积累。P53突变与分期直接相关，与MSI-H呈负相关。远端CRC在主要的CpG热点密码子处更频繁发生突变[248（8/66，12.1%）、175（7/66，10.6%）和245（7/66，10.6%）]，而在近端肿瘤中，密码子213成为最常发生突变的位点（5/28，17.9% 对比 3/66，4.5%，P = 0.048）。CpG位点的转换是最常见的突变类型，在非黏液性肿瘤中更频繁（25% 对比黏液性肿瘤中的10.4%，P = 0.032），在远端CRC中也更频繁（27% 对比近端CRC中的12.5%，P = 0.02），并且与K-ras颠换相关。非CpG位点的转换是第二常见的P53突变类型，在近端肿瘤中更频繁（15.6% 对比远端肿瘤中的4.7%，P = 0.01），并且与K-ras转换和MSI-H相关。总体突变频率和类型以及与P53积累、分期和MSI-H的相关性与非伊朗患者的报道一致。然而，近端和远端CRC的P53突变位点/类型以及P53与K-ras突变类型之间的相关性有所不同。近端CRC中反复出现的密码子213 P53突变先前在伊朗北部的食管癌中也被报道为常见。
