O6-methyl-guanine-DNA methyltransferase methylation and IDH1/2 mutation in small cell lung cancer

Abstract

Abstract. Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O 6 -methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. In order to identify the status of MGMT promoter methylation and IDH1/2 mutation of SCLC in China, 33 SCLC specimens from patients that underwent surgery were retrospectively collected in Zhejiang Cancer Hospital (Hangzhou, China) between 2008 and 2014. High-resolution melting analysis and methylation-specific polymerase chain reaction were used to detect MGMT promoter methylation, and polymerase chain reaction amplification and Sanger sequencing were utilized to detect IDH1/2 mutation. Of the 33 examined SCLC specimens, MGMT promoter methylation was detected in 17 patients (51.5%), and no IDH1/2 mutations were detected in the analyzed samples. These findings indicate that the IDH1/2 mutation may not be an ideal marker in SCLC patients treated with temozolomide. Future studies on the predictive and prognostic value of MGMT promoter methylation are urgently required for patients with relapsed SCLC treated with temozolomide in China.

Are anaplastic lymphoma kinase (ALK) and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation driver biomarkers of pulmonary neuroendocrine tumors (NETs) and carcinomas (NECs)?

“…In another study, 17 out of 33 Chinese SCLC patients (51.5%) had MGMT promoter methylation [ 38 ]. A comparative study between temozolomide and veliparib versus temozolomide with placebo in patients with relapsed SCLC did not show improved progression free survival [ 39 ].…”

MGMT promoter methylation and 1p/19q co-deletion of surgically resected pulmonary carcinoid and large-cell neuroendocrine carcinoma

“…TMZ-based chemotherapy is recommended as first- or second-line treatment for TC or AC with negative somatostatin receptor (SSR) and rapid progression [ 31 ]. In our previous report, 33 SCLC specimens obtained from surgery were collected retrospectively and analyzed by high-resolution melting (HRM) analysis and methylation-specific polymerase chain reaction (MSP); MGMT promoter methylation was detected in 17 patients (51.5%) [ 32 ]. 1p/19q co-deletion was found in three patients, who survived after 58, 50, and 30 months of follow-up comprising of 32 SCLC resected specimens, thereby indicating a good prognostic factor in SCLC [ 10 ].…”

mRNA Expression of FGFR1 as Potential Marker for Predicting Prognosis of Surgical Resection of Small Cell Lung Cancer may be better than Protein Expression and Gene Amplification

“…Formalin-fixed paraffin-embedded tumor samples were obtained from a unique series of 33 patients with SCLC, who underwent pulmonary resection between April 2008 and June 2014 at Zhejiang Cancer Hospital (Hangzhou, China) [13]. Three patients underwent pneumonectomy with lymph node dissection, one patient received wedge resection with lymph node dissection, and 29 patients received lobectomy with lymph node dissection.…”

“…All patients were diagnosed with conventional SCLC, and the pathological diagnosis was based on the standard criteria defined by WHO classification [14]. Specimens from 33 patients were subjected to immunohistochemistry (IHC), polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR) and medical records were reviewed to obtain clinical characteristics, including gender, age, smoking status, tumor stage, referring to our previous published research [13]. Furthermore 28/33 were subjected to fluorescence in-situ hybridization (FISH) analysis, and medical records were reviewed to assimilate the clinical characteristics, including gender, age, smoking status, tumor stage ( Table 1).…”