Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis

Clin Transl Oncol. 2012 Jan;14(1):31-5. doi: 10.1007/s12094-012-0758-6.

Abstract

Background: O6-methylguanine-DNA-methyl transferase (MGMT), a DNA repair gene, is a key enzyme for predicting the response to both radiotherapy and temozolomide in glioma patients. Data on the MGMT promoter methylation status in relation to the time to develop intracranial new metastasis or local relapse at the surgical site after brain surgery followed by radiotherapy is limited in non-small-cell lung cancer (NSCLC) patients with a single brain metastasis.

Methods: All 55 patients included in this analysis were NSCLC with a single brain metastasis and had undergone brain surgery followed by radiotherapy. Genomic DNA was extracted from the brain tumour. The DNA was treated with bisulphate and a methylation-specific polymerase chain reaction was performed. Survival was compared by the status of promoter region of MGMT.

Results: The time to develop intracranial new metastases or local relapse at the surgical site after treatment in patients with methylation of the MGMT promoter region was 4.0 months (N = 5), while that of the patients without methylation of the MGMT promoter region was 11.5 months (N = 50) (p = 0.37).

Conclusions: NSCLC patients with brain metastasis treated by brain surgery followed by radiotherapy may have a higher chance of relapse when the tumour has methylation of the MGMT promoter region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / secondary
  • Carcinoma, Large Cell / therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Combined Modality Therapy
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Radiotherapy Dosage
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*

Substances

  • DNA, Neoplasm
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes