K-ras, BRCA1/2, and CHEK2 mutations and loss of heterozygosity at 9p, 17p, and 18q in sporadic adenocarcinoma of the pancreas
K-ras, BRCA1/2, and CHEK2 mutations and loss of heterozygosity at 9p, 17p, and 18q in sporadic adenocarcinoma of the pancreas
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DOI：
10.1134/s0026893309030054
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发表时间：
2009-06-01
影响因子：
1.2
通讯作者：
Kalinin, V. N.
中科院分区：
文献类型：
--
作者：
Amosenko, F. A.;Kazubskaya, T. P.;Kalinin, V. N.
评估了分子标记的诊断意义，包括 K-ras、TP53、CDKN2A 和 MADH4 基因座最常见的体细胞畸变，以及胰腺散发性腺癌侵袭前阶段出现的 BRCA1、BRCA2 和 CHEK2 的不太常见突变。该研究是对取自 37 名俄罗斯患者的原发性胰腺癌和正常胰腺组织标本进行的。对手术腺癌标本进行手动显微切割。在 24 个肿瘤标本中发现了 K-ras 密码子 12 的突变（0.65），但在正常胰腺组织标本中没有发现。未发现 BRCA1（185delAG、300T > G、4153delA、4158A > G、5382insC）、BRCA2（695insT、6174delT）和 CHEK2（1100delC）突变。等位基因丢失的信息量在三个抑癌基因座之间没有显着差异，TP53 (GDB186817) 和 CDKN2A (D9S974 + D9S162) 的等位基因丢失的信息量为 60%，MADH4 (D18S363 + D18S474) 的等位基因丢失的信息量为 65.7% (t = 0.48)。 CDKN2A 基因座的 LOH 频率最高，为 0.95。对于 TP53 和 MADH4，LOH 频率分别为 0.62 和 0.70。在 80% 的腺癌中，至少有一个位点具有 LOH。 K-ras 突变和 9p、17p 和 18q 杂合性缺失的综合数据的总体信息率为 85.7%。只有 9% 的肿瘤具有微卫星不稳定性。
The diagnostic significance of molecular markers was assessed for the most common somatic aberrations at the K-ras, TP53, CDKN2A, and MADH4 loci, as well as less common mutations of BRCA1, BRCA2, and CHEK2, arising in preinvasive stages of sporadic adenocarcinoma of the pancreas. The study was performed on paired primary pancreatic adenocarcinoma and normal pancreatic tissue specimens obtained from 37 Russian patients. Surgical adenocarcinoma specimens were subjected to manual microdissection. Mutations of K-ras codon 12 were found in 24 tumor specimens (0.65), but not in normal pancreatic tissue specimens. Mutations of BRCA1 (185delAG, 300T > G, 4153delA, 4158A > G, 5382insC), BRCA2 (695insT, 6174delT), and CHEK2 (1100delC) were not found. The informativeness of allelic losses did not differ significantly among the three tumor suppressor loci and was 60% for TP53 (GDB186817) and CDKN2A (D9S974 + D9S162) and 65.7% for MADH4 (D18S363 + D18S474) (t = 0.48). The CDKN2A locus had the highest LOH frequency of 0.95. For TP53 and MADH4 the LOH frequency was 0.62 and 0.70, respectively. In 80% of adenocarcinomas, at least one locus was characterized with LOH. The overall informativeness of the combined data on K-ras mutations and loss of heterozygosity at 9p, 17p, and 18q was 85.7%. Only 9% of the tumors were characterized with microsatellite instability.