Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma
Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma
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DOI：
10.1200/jco.2006.08.0283
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发表时间：
2007-02-20
影响因子：
45.3
通讯作者：
Ajani, Jaffer A.
中科院分区：
文献类型：
--
作者：
Izzo, Julie G.;Wu, Tsung-Teh;Ajani, Jaffer A.
目的改变的细胞周期蛋白 D1 (CD1) 是一种细胞周期调节因子，可能在赋予食管腺癌 (EAC) 侵袭性方面发挥重要作用。 CD1 基因单核苷酸多态性 G/A870 产生两个选择性剪接的转录本：CD1a 和 CD1b。 CD1b 主要由 A870 等位基因编码，被认为具有致癌性。我们假设 CD1 A870 等位基因与较高的 CD1 蛋白表达相关，并在 EAC 进化过程中增加基因组不稳定性，从而导致更具攻击性的表型。 患者和方法 对 124 个 EAC 档案标本和 39 个相关的 Barrett 食管 (BE) 标本进行了 CD1 基因型、CD1 蛋白表达和 9 号染色体多体性（代表基因组不稳定性）的检查。我们将 CD1 基因型与 CD1 蛋白表达、基因组不稳定性、诊断 EAC 时的年龄以及总生存期 (OS) 相关联。结果 A870 等位基因与 EAC 中较高水平的 CD1 蛋白表达相关 ( P =.032)；在 BE (P =.01) 中，它与伴随的 9 号染色体多体性增加相关 (P =.002)；且诊断时年龄较小（ P
PurposeAltered cyclin D1 (CD1), a cell cycle regulator, may play an important role in imparting aggressive nature to esophageal adenocarcinoma (EAC). CD1 gene single nucleotide polymorphism G/A870 results in two alternatively spliced transcripts, CD1a and CD1b. CD1b, preferentially encoded by the A870 allele, is putatively oncogenic. We hypothesized that CD1 A870 allele would be associated with higher CD1 protein expression, and increased genomic instability during EAC evolution, leading to more aggressive phenotype.Patients and MethodsOne hundred twenty-four archival specimens of EAC, and 39 associated Barrett's esophagus ( BE) specimens were examined for CD1 genotype, CD1 protein expression, and chromosome 9 polysomy ( representing genomic instability). We correlated CD1 genotypes with CD1 protein expression, genomic instability, age at diagnosis of EAC, and overall survival ( OS).ResultsThe A870 allele was associated with higher levels of CD1 protein expression in EAC ( P =.032); in BE ( P =.01) where it was associated with concomitant increased chromosome 9 polysomy ( P =.002); and with a younger age at diagnosis ( P