Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma

Chen Sung Lin, Liang Shun Wang, Shi Chuan Chang, Teh Ying Chou, Wen Hu Hsu, Chin San Liu, Mau Hwa Lee, Ming Yi Chung, Yau Huei Wei

Research output: Contribution to journalArticle

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Abstract

We investigated the microsatellite alterations in mitochondrial DNA (mtDNA) and in TP53 in thoracic esophageal squamous cell carcinomas (TESCC). Using laser microdissection, 66 paired non-cancerous esophageal muscles, non-cancerous esophageal mucosa, cancerous TESCC nests plus 35 metastatic lymph nodes harvested from 66 resected esophagi of TESCC patients were subjected to DNA extraction. D310 and D17S960 were chosen as markers to address microsatellite alterations in mtDNA, including changes in copy number and homoplasmic/ heteroplasmic mutations of mtDNA, and in TP53, including loss of heterozygosity (LOH) and microsatellite instability (MI). From non-cancerous esophageal mucosa to cancerous TESCC nests and then metastatic lymph nodes, a trend of homoplasmic D310 mutation (10.6, 25.8, 31.4%; P=0.023), an ever increase of mtDNA copy ratios (0.892, 1.128, 1.183; P=0.018) and an elevated incidence of TP53 LOH (19.7, 34.8, 37.1%; P=0.010) were observed. From T1, T2, T3 to T4 TESCC, the incidence of TP53 LOH (12.5, 16.7, 34.8, 52.2%; P=0.011) was increased, in a stepwise fashion. Furthermore, we observed an association of TP53 LOH with an increased mtDNA copy ratio (P=0.022) and TP53 MI with heteroplasmic D310 mutation (P=0.069) in TESCC. Concurrent and associated microsatellite alterations in mtDNA and in TP53 in TESCC support the cancer clonal expansion theory and imply a possible relationship between the mitochondria and p53 in TESCC.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalOncology Reports
Volume28
Issue number1
DOIs
Publication statusPublished - Jul 2012

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Mitochondrial DNA
Microsatellite Repeats
Thorax
Loss of Heterozygosity
Microsatellite Instability
Mutation
Lymph Nodes
Microdissection
Esophageal Squamous Cell Carcinoma
Incidence
Esophagus
Mitochondria
Lasers
Muscles
DNA
Neoplasms

Keywords

  • Heteroplasmy
  • Loss of heterozygosity
  • Microsatellite instability
  • Mitochondrial DNA
  • Thoracic esophageal squamous cell carcinoma
  • TP53 gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lin, C. S., Wang, L. S., Chang, S. C., Chou, T. Y., Hsu, W. H., Liu, C. S., ... Wei, Y. H. (2012). Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma. Oncology Reports, 28(1), 69-76. https://doi.org/10.3892/or.2012.1761

Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma. / Lin, Chen Sung; Wang, Liang Shun; Chang, Shi Chuan; Chou, Teh Ying; Hsu, Wen Hu; Liu, Chin San; Lee, Mau Hwa; Chung, Ming Yi; Wei, Yau Huei.

In: Oncology Reports, Vol. 28, No. 1, 07.2012, p. 69-76.

Research output: Contribution to journalArticle

Lin, CS, Wang, LS, Chang, SC, Chou, TY, Hsu, WH, Liu, CS, Lee, MH, Chung, MY & Wei, YH 2012, 'Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma', Oncology Reports, vol. 28, no. 1, pp. 69-76. https://doi.org/10.3892/or.2012.1761
Lin, Chen Sung ; Wang, Liang Shun ; Chang, Shi Chuan ; Chou, Teh Ying ; Hsu, Wen Hu ; Liu, Chin San ; Lee, Mau Hwa ; Chung, Ming Yi ; Wei, Yau Huei. / Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma. In: Oncology Reports. 2012 ; Vol. 28, No. 1. pp. 69-76.
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abstract = "We investigated the microsatellite alterations in mitochondrial DNA (mtDNA) and in TP53 in thoracic esophageal squamous cell carcinomas (TESCC). Using laser microdissection, 66 paired non-cancerous esophageal muscles, non-cancerous esophageal mucosa, cancerous TESCC nests plus 35 metastatic lymph nodes harvested from 66 resected esophagi of TESCC patients were subjected to DNA extraction. D310 and D17S960 were chosen as markers to address microsatellite alterations in mtDNA, including changes in copy number and homoplasmic/ heteroplasmic mutations of mtDNA, and in TP53, including loss of heterozygosity (LOH) and microsatellite instability (MI). From non-cancerous esophageal mucosa to cancerous TESCC nests and then metastatic lymph nodes, a trend of homoplasmic D310 mutation (10.6, 25.8, 31.4{\%}; P=0.023), an ever increase of mtDNA copy ratios (0.892, 1.128, 1.183; P=0.018) and an elevated incidence of TP53 LOH (19.7, 34.8, 37.1{\%}; P=0.010) were observed. From T1, T2, T3 to T4 TESCC, the incidence of TP53 LOH (12.5, 16.7, 34.8, 52.2{\%}; P=0.011) was increased, in a stepwise fashion. Furthermore, we observed an association of TP53 LOH with an increased mtDNA copy ratio (P=0.022) and TP53 MI with heteroplasmic D310 mutation (P=0.069) in TESCC. Concurrent and associated microsatellite alterations in mtDNA and in TP53 in TESCC support the cancer clonal expansion theory and imply a possible relationship between the mitochondria and p53 in TESCC.",
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