The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma

• Main Authors: Djos Anna, Martinsson Tommy, Kogner Per, Carén Helena
• Format: Article
• Language: English
• Published: BMC 2012-06-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/11/1/40

<p>Abstract</p> <p>Background</p> <p>Hypermethylation of promotor CpG islands is a common mechanism that inactivates tumor suppressor genes in cancer. Genes belonging to the <it>RASSF</it> gene family have frequently been reported as epigenetically silenced by promotor methylation in human cancers. Two members of this gene family, <it>RASSF1A</it> and <it>RASSF5A</it> have been reported as methylated in neuroblastoma. Data from our previously performed genome-wide DNA methylation array analysis indicated that other members of the <it>RASSF</it> gene family are targeted by DNA methylation in neuroblastoma.</p> <p>Results</p> <p>In the current study, we found that several of the <it>RASSF</it> family genes (<it>RASSF2</it>, <it>RASSF4</it>, <it>RASSF5</it>, <it>RASSF6</it>, <it>RASSF7</it>, and <it>RASSF10</it>) to various degrees were methylated in neuroblastoma cell lines and primary tumors. In addition, several of the <it>RASSF</it> family genes showed low or absent mRNA expression in neuroblastoma cell lines. <it>RASSF5</it> and <it>RASSF6</it> were to various degrees methylated in a large portion of neuroblastoma tumors and <it>RASSF7</it> was heavily methylated in most tumors. Further, CpG methylation sites in the CpG islands of some <it>RASSF</it> family members could be used to significantly discriminate between biological subgroups of neuroblastoma tumors. For example, <it>RASSF5</it> methylation highly correlated to <it>MYCN</it> amplification and INRG stage M. Furthermore, high methylation of <it>RASSF6</it> was correlated to unfavorable outcome, 1p deletion and <it>MYCN</it> amplification in our tumor material.</p> <p>In conclusion</p> <p>This study shows that several genes belonging to the <it>RASSF</it> gene family are methylated in neuroblastoma. The genes <it>RASSF5</it>, <it>RASSF6</it> and <it>RASSF7</it> stand out as the most promising candidate genes for further investigations in neuroblastoma.</p>