Copy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewers.
Oral squamous cell carcinoma (OSCC) is a worldwide disease. In South Asians, the high prevalence of OSCC is tightly linked to areca chewing. The prognosis for OSCC remains dismal and improvement in early diagnosis may benefit the survival of patients with this disease. Chromosome region 3q26-27 has been shown to carry several oncogenes. By quantitative PCR (Q-PCR), the gene copy numbers of TERC, PI3KCA, ZASC1, and TP63 from microdissected OSCCs have been determined. Copy number amplifications of PI3KCA and ZASC1, a newly identified zinc finger transcription factor, were identified in 30 (65%) and 32 (70%) of 46 primary OSCCs, respectively. Co-amplification of PI3KCA and ZASC1 in 50% of primary OSCCs suggests that they are critical targets of the 3q26.3 amplicon. OSCCs carrying higher levels of PI3KCA and/or ZASC1 copy number amplification were associated with a significantly higher propensity for lymph node metastasis. ZASC1 mRNA expression in OSCC was also associated with lymph node metastasis. In addition, copy number amplification of at least one 3q26-27 oncogene was detected in brush samples from 10 of 22 (45%) patients with oral leukoplakia and 5 of 20 (25%) oral mucosa samples from areca chewers without a visible lesion. These data indicate frequent copy number amplification and overexpression of ZASC1 in OSCC. The findings also suggest the potential use of Q-PCR analysis and brush collection of samples to dissect OSCC risk.
Lin
Shu-Chun
SC
School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Liu
Chung-Ji
CJ
Ko
Shun-Yao
SY
Chang
Hsiao-Ching
HC
Liu
Tsung-Yun
TY
Chang
Kuo-Wei
KW
D000328:Adult; D001114:Areca / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000556:secondary; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C479231:ZNF639 protein, human; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase