Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, PA, USA.
Mod Pathol. 2011 Dec;24(12):1571-7. doi: 10.1038/modpathol.2011.109. Epub 2011 Jul 8.
The significance of KRAS mutant allele-specific imbalance (MASI) in lung adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant allele over the wild-type allele. We assessed the frequency of KRAS MASI by comparing peak heights of mutant and wild-type alleles on sequencing electropherograms and by KRAS fluorescence in situ hybridization (FISH). A review of sequencing electropherograms of 207 KRAS-mutated lung adenocarcinomas demonstrated 23 (11%) cases with the mutant allele peak higher than the wild-type allele peak and 15 (7%) cases with the mutant allele peak equal to the wild-type allele peak. Of 17 cases with the mutant allele peak higher or equal to the wild-type allele peak, 8 (47%) showed KRAS amplification by FISH. KRAS FISH analysis of 36 KRAS-mutated lung adenocarcinomas with the mutant allele peak lower than the wild-type allele peak, 21 KRAS and EGFR wild-type and 16 EGFR-mutated adenocarcinomas showed no KRAS amplification. KRAS MASI was associated with selective amplification of the KRAS mutant allele (P<0.001). Patients with KRAS MASI showed worse overall survival. The cumulative proportion surviving at 17 months for KRAS MASI group was 35% compared with 84.1% for patients with KRAS mutant allele peak lower than wild-type allele peak (P=0.012). The adverse prognostic significance of KRAS MASI was independent of clinical stage and was maintained among stage I patients. The detection of KRAS MASI in lung adenocarcinomas by sequencing electropherograms may identify patients with more aggressive disease.
KRAS 突变等位基因特异性不平衡 (MASI) 在肺腺癌中的意义尚不清楚。KRAS MASI 的定义为突变等位基因相对于野生型等位基因的优势。我们通过比较测序电泳图谱中突变和野生型等位基因的峰高以及 KRAS 荧光原位杂交 (FISH) 来评估 KRAS MASI 的频率。对 207 例 KRAS 突变肺腺癌测序电泳图谱的回顾性分析显示，23 例（11%）病例的突变等位基因峰高于野生型等位基因峰，15 例（7%）病例的突变等位基因峰等于野生型等位基因峰。在突变等位基因峰高于或等于野生型等位基因峰的 17 例病例中，8 例（47%）通过 FISH 显示 KRAS 扩增。对突变等位基因峰低于野生型等位基因峰的 36 例 KRAS 突变肺腺癌进行 KRAS FISH 分析，21 例 KRAS 和 EGFR 野生型和 16 例 EGFR 突变腺癌未见 KRAS 扩增。KRAS MASI 与 KRAS 突变等位基因的选择性扩增相关（P<0.001）。KRAS MASI 患者的总生存期较差。KRAS MASI 组患者在 17 个月时的累积生存率为 35%，而 KRAS 突变等位基因峰低于野生型等位基因峰的患者为 84.1%（P=0.012）。KRAS MASI 的不良预后意义独立于临床分期，并在 I 期患者中保持不变。通过测序电泳图谱检测肺腺癌中的 KRAS MASI 可能有助于识别更具侵袭性的疾病患者。
