Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Int J Cancer. 2012 Oct 15;131(8):1810-7. doi: 10.1002/ijc.27461. Epub 2012 Mar 22.
The prognostic impact of distinct KRAS mutations in colorectal carcinomas is not fully characterized. We hypothesized that the prognostic impact of KRAS mutations is modulated by KRAS mutant allele-specific imbalance (MASI). KRAS MASI was assessed by sequencing electropherograms in KRAS-mutated colorectal carcinomas (N = 394, prospectively tested). The mechanism of KRAS MASI was studied by fluorescence in situ hybridization (FISH; N = 50). FISH showed that KRAS MASI developed by chromosome 12 hyperploidy (9/18, 50%) or KRAS amplification (1/18, 5.5%). KRAS MASI was more common in tumors with KRAS codon 13 than with codon 12 mutations [24/81, 30% vs. 54/313, 17%; odds ratio (OR), 2.0, 95% confidence interval (CI), 1.2-3.5; p = 0.01]. KRAS MASI was correlated with overall survival (N = 358, median follow-up = 21 months). In a multivariate analysis, KRAS codon 13 MASI was an independent adverse prognostic factor (compared to codon 13 mutants without MASI combined with all codon 12 mutants; adjusted hazard ratio, 2.2, 95% CI: 1.2-3.9; p = 0.01). KRAS MASI arises through chromosome 12 hyperploidy or KRAS amplification and, when affects KRAS codon 13, is associated with worse overall survival.
不同 KRAS 突变在结直肠癌中的预后影响尚未完全明确。我们假设 KRAS 突变的预后影响受到 KRAS 突变等位基因特异性失衡（MASI）的调节。通过对 KRAS 突变的结直肠癌（前瞻性检测，N = 394）的 KRAS 突变等位基因特异性失衡（MASI）进行测序电泳图谱评估。通过荧光原位杂交（FISH；N = 50）研究 KRAS MASI 的机制。FISH 显示，KRAS MASI 通过 12 号染色体的三倍体（9/18，50%）或 KRAS 扩增（1/18，5.5%）发展。KRAS MASI 在 KRAS 密码子 13 突变的肿瘤中比在密码子 12 突变的肿瘤中更常见[24/81，30%比 54/313，17%；比值比（OR），2.0，95%置信区间（CI），1.2-3.5；p = 0.01]。KRAS MASI 与总生存相关（N = 358，中位随访时间 = 21 个月）。在多变量分析中，KRAS 密码子 13 MASI 是独立的不良预后因素（与无 MASI 的 KRAS 密码子 13 突变体和所有 KRAS 密码子 12 突变体相比；调整后的危险比，2.2，95%CI：1.2-3.9；p = 0.01）。KRAS MASI 通过 12 号染色体的三倍体或 KRAS 扩增而产生，当影响 KRAS 密码子 13 时，与总体生存率降低相关。
