Abstract:

OBJECTIVE: The aim of this study is to clarify genome-wide DNA methylation profiles in renal tumors of various histological subtypes.
METHODS: Bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using tissue samples of 17 patients with papillary renal cell carcinomas (RCCs), chromophobe RCCs and oncocytomas, and the results were compared with those from 51 patients with clear cell RCCs.
RESULTS: Unsupervised hierarchical clustering analysis based on DNA methylation status clustered type 1 and type 2 papillary RCCs into different subclasses. Although chromophobe RCCs and oncocytomas were clustered into the same subclass, the DNA methylation status of 21 BAC clones was able to discriminate chromophobe RCCs from oncocytomas. The number of BAC clones showing DNA methylation alteration in non-tumorous renal tissue from patients with chromophobe RCCs and oncocytomas was smaller than that from patients with clear cell RCCs. Biphasic accumulation of DNA methylation alterations was observed in non-tumorous renal tissue from all 68 patients, and patients showing such alterations on more BAC clones had a poorer outcome than patients showing them on fewer BAC clones.
CONCLUSIONS: DNA methylation profiles determining the histological subtypes of renal tumors developing in individual patients and/or patient outcome may be already established in non-tumorous renal tissue at the precancerous stage.

日本語要旨:

ゲノム網羅的DNAメチル化解析で、淡明細胞がん・乳頭状腎細胞がん・嫌色素細胞がん・オンコサイトーマ等の組織型と症例の予後を規定するDNAメチル化プロファイルが、腎の前がん段階で既に成立していることを示した。