Yunxia Ma1, Yuan Chen1, Iver Petersen2. 1. Institute of Pathology, University Hospital Jena, Friedrich Schiller University Jena, Ziegelmuehlenweg 1, 07740 Jena, Germany. 2. Institute of Pathology, University Hospital Jena, Friedrich Schiller University Jena, Ziegelmuehlenweg 1, 07740 Jena, Germany. Electronic address: iver.petersen@med.uni-jena.de.
Abstract
AIMS: Aberrant DNA methylation is a common molecular feature in human cancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in human colorectal and lung cancer and to evaluate its clinical relevance. METHODS: The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancer patient samples. In cancer cell lines, the methylation status of MLH1 promoter and exon 2 was investigated by bisulfite sequencing (BS). Methylation-specific-PCR (MSP) was used to evaluate methylation status of MLH1. RESULTS: The expression of MLH1 mRNA was detected in 8 CRC cell lines as well as normal colonic fibroblast cells CCD-33Co. At protein levels, MLH1 was lost in one CRC cell line HCT-116 and normal cells CCD-33Co. No methylation was found in the promoter and exon 2 of MLH1 in CRC cell lines. MLH1 was expressed in 8 lung cancer cell lines at both mRNA and protein levels. Compared to cancer cells, normal bronchial epithelial cells (HBEC) had lower expression of MLH1 protein. In primary CRC, 54.5% of cases exhibited positive staining, while 47.8% of lung tumors were positive for MLH1 protein. MSP analysis showed that 58 out of 92 (63.0%) CRC and 41 out of 73 (56.2%) lung cancer exhibited MLH1 methylation. In CRC, the MLH1 methylation was significantly associated with tumor invasion in veins (P=0.012). However, no significant links were found between MLH1 expression and promoter methylation in both tumor entities. CONCLUSIONS: MLH1 methylation is a frequent molecular event in CRC and lung cancer patients. In CRC, methylation of MLH1 could be linked to vascular invasiveness.
AIMS: Aberrant DNA methylation is a common molecular feature in humancancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in humancolorectal and lung cancer and to evaluate its clinical relevance. METHODS: The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancerpatient samples. In cancer cell lines, the methylation status of MLH1 promoter and exon 2 was investigated by bisulfite sequencing (BS). Methylation-specific-PCR (MSP) was used to evaluate methylation status of MLH1. RESULTS: The expression of MLH1 mRNA was detected in 8 CRC cell lines as well as normal colonic fibroblast cells CCD-33Co. At protein levels, MLH1 was lost in one CRC cell line HCT-116 and normal cells CCD-33Co. No methylation was found in the promoter and exon 2 of MLH1 in CRC cell lines. MLH1 was expressed in 8 lung cancer cell lines at both mRNA and protein levels. Compared to cancer cells, normal bronchial epithelial cells (HBEC) had lower expression of MLH1 protein. In primary CRC, 54.5% of cases exhibited positive staining, while 47.8% of lung tumors were positive for MLH1 protein. MSP analysis showed that 58 out of 92 (63.0%) CRC and 41 out of 73 (56.2%) lung cancer exhibited MLH1 methylation. In CRC, the MLH1 methylation was significantly associated with tumor invasion in veins (P=0.012). However, no significant links were found between MLH1 expression and promoter methylation in both tumor entities. CONCLUSIONS:MLH1 methylation is a frequent molecular event in CRC and lung cancerpatients. In CRC, methylation of MLH1 could be linked to vascular invasiveness.
Authors: Rutulkumar Patel; Luchang Zhang; Amar Desai; Mark J Hoenerhoff; Lucy H Kennedy; Tomas Radivoyevitch; Chiara La Tessa; Stanton L Gerson; Scott M Welford Journal: Int J Radiat Oncol Biol Phys Date: 2020-07-04 Impact factor: 7.038
Authors: Salsabeel H Sabi; Omar F Khabour; Karem H Alzoubi; Caroline O Cobb; Thomas Eissenberg Journal: Inhal Toxicol Date: 2020-04-22 Impact factor: 2.724