Lai Liang-Chuan, Tsai Mong-Hsun, Chen Pei-Chun, Chen Lee H, Hsiao Jen-Hao, Chen Shin-Kuang, Lu Tzu-Pin, Lee Jang-Ming, Hsu Chung-Ping, Hsiao Chuhsing K, Chuang Eric Y
Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
J Biomed Sci. 2014 Mar 21;21(1):24. doi: 10.1186/1423-0127-21-24.
Numerous efforts have been made to elucidate the etiology and improve the treatment of lung cancer, but the overall five-year survival rate is still only 15%. Although cigarette smoking is the primary risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. Since cancer results from progressive accumulation of genetic aberrations, genomic rearrangements may be early events in carcinogenesis.
In order to identify biomarkers of early-stage adenocarcinoma, the genome-wide DNA aberrations of 60 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined using Affymetrix Genome-Wide Human SNP 6.0 arrays. Common copy number variation (CNV) regions were identified by ≥30% of patients with copy number beyond 2 ± 0.5 of copy numbers for each single nucleotide polymorphism (SNP) and at least 100 continuous SNP variant loci. SNPs associated with lung adenocarcinoma were identified by McNemar's test. Loss of heterozygosity (LOH) SNPs were identified in ≥18% of patients with LOH in the locus. Aberration of SNP rs10248565 at HDAC9 in chromosome 7p21.1 was identified from concurrent analyses of CNVs, SNPs, and LOH.
The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 may be a potential biomarker of cancer susceptibility.
人们已做出诸多努力来阐明肺癌的病因并改善其治疗方法，但总体五年生存率仍仅为15%。尽管吸烟是肺癌的主要危险因素，但台湾只有7%的女性肺癌患者有吸烟史。由于癌症是由基因畸变的逐步积累导致的，基因组重排可能是致癌过程中的早期事件。
为了鉴定早期腺癌的生物标志物，使用Affymetrix全基因组人类SNP 6.0芯片检测了60对非吸烟女性肺腺癌及相邻正常肺组织的全基因组DNA畸变。通过每个单核苷酸多态性（SNP）拷贝数超过2±0.5的拷贝数且至少有100个连续SNP变异位点的患者中≥30%来确定常见拷贝数变异（CNV）区域。通过McNemar检验鉴定与肺腺癌相关的SNP。在该位点杂合性缺失（LOH）≥18%的患者中鉴定出LOH SNP。通过对CNV、SNP和LOH的同步分析，在7号染色体p21.1区域的HDAC9基因座中鉴定出SNP rs10248565的畸变。
结果表明SNP rs10248565可能是癌症易感性的潜在生物标志物，从而阐明了肺腺癌的遗传病因。
