BACKGROUND: Little is known about the dual role of RAS-association domain family 1 (RASSF1) gene at 3p21.3 in neuroendocrine tumors (NET) of the lung. MATERIALS AND METHODS: Twenty typical carcinoids (TC), 11 atypical carcinoids (ATC), 11 large cell neuroendocrine carcinomas (LCNEC) and 16 small cell lung carcinomas (SCLC) were analyzed for RASSF1 promoter methylation, mRNA and protein expression, and loss of 3p21.3 locus. RESULTS: Promoter 1 was hypermethylated in NET but not in paired non-neoplastic lung tissues nor in 20 control NSCLC, with the degree of hypermethylation paralleling tumor grade. RASSF1 A/E isoform mRNA but not protein expression was lost in most NET compared to NSCLC or non-neoplastic tissues. The relationship between methylation level and mRNA or protein loss varied by NET type, with significant correlation for decreasing RASSF1 A protein in ACT, and marginal correlation for down-regulated RASSF 1 A/E mRNA in TC, this suggesting a non linear regulation by methylation in NET. No promoter 2 methylation was detected in NET; however, up-regulation of its RASSF1 C transcript emerged as an adverse prognostic factor in the LCNEC/SCLC group. A correlation was found between 3p21.3 allelic loss and decrease of RASSF1 A/E mRNA (p=0.023) and protein (p=0.043) expression in ATC, suggesting that 3p21.3 allelic loss contributed to the loss of gene expression. CONCLUSION: RASSF1 A/E is likely to act as a tumor suppressor gene in most pulmonary NET, and RASSF1 C as an oncogene in high-grade tumors.
BACKGROUND: Little is known about the dual role of RAS-association domain family 1 (RASSF1) gene at 3p21.3 in neuroendocrine tumors (NET) of the lung. MATERIALS AND METHODS: Twenty typical carcinoids (TC), 11 atypical carcinoids (ATC), 11 large cell neuroendocrine carcinomas (LCNEC) and 16 small cell lung carcinomas (SCLC) were analyzed for RASSF1 promoter methylation, mRNA and protein expression, and loss of 3p21.3 locus. RESULTS: Promoter 1 was hypermethylated in NET but not in paired non-neoplastic lung tissues nor in 20 control NSCLC, with the degree of hypermethylation paralleling tumor grade. RASSF1 A/E isoform mRNA but not protein expression was lost in most NET compared to NSCLC or non-neoplastic tissues. The relationship between methylation level and mRNA or protein loss varied by NET type, with significant correlation for decreasing RASSF1 A protein in ACT, and marginal correlation for down-regulated RASSF 1 A/E mRNA in TC, this suggesting a non linear regulation by methylation in NET. No promoter 2 methylation was detected in NET; however, up-regulation of its RASSF1 C transcript emerged as an adverse prognostic factor in the LCNEC/SCLC group. A correlation was found between 3p21.3 allelic loss and decrease of RASSF1 A/E mRNA (p=0.023) and protein (p=0.043) expression in ATC, suggesting that 3p21.3 allelic loss contributed to the loss of gene expression. CONCLUSION:RASSF1 A/E is likely to act as a tumor suppressor gene in most pulmonary NET, and RASSF1 C as an oncogene in high-grade tumors.
Authors: Patrick Kwok Shing Ng; Carol Po Ying Lau; Emily Kai Yee Lam; Sheila Sai Kam Li; Vivian Wai Yan Lui; Winnie Yeo; Yuen Keng Ng; Paul Bo San Lai; Stephen Kwok Wing Tsui Journal: Dig Dis Sci Date: 2018-01-20 Impact factor: 3.199
Authors: Jaroslaw Jendrzejewski; Huiling He; Hanna S Radomska; Wei Li; Jerneja Tomsic; Sandya Liyanarachchi; Ramana V Davuluri; Rebecca Nagy; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2012-05-14 Impact factor: 11.205
Authors: Mark E Reeves; Melissa L Baldwin; Robert Aragon; Scott Baldwin; Shin-Tai Chen; Xinmin Li; Subburaman Mohan; Yousef G Amaar Journal: BMC Res Notes Date: 2012-05-16