KS1 (KRAB suppressor of transformation 1) and BMP3b (bone morphogenetic protein 3b) gene promoter hypermethylation is a common epigenetic event in breast cancer

Abstract

9608 Background: KS1 (KRAB Suppressor of Transformation 1) is a member of the Krüppel-associated box-zinc finger proteins (KRAB-ZFPs). Indirect evidence suggests that KS1 is a tumor suppressor gene. The Bone Morphogenetic Protein 3b (BMP3b), also known as GDF10, localizes to chromosome 10q11.1, a region of LOH in several cancers. This gene has putative tumor suppressor functions, being hypermethylated and down-regulated in lung cancers. We present here evidence that the KS1 and BMP3b genes are hypermethylated in breast cancer and not in normal breast tissues. We also present data to show methylation of KS1 in benign breast disease (BBD). Goals: We designed this study to find methylated genes in breast cancer and BBD with the goal of finding markers with potential for risk prediction/early detection of breast cancer. Methods: Aberrant promoter methylation of KS1 and BMP3b was studied by methylation-specific PCR using bisulfite treated DNA from 45 frozen breast cancer samples,12 normal controls, 5 paraffin embedded benign breast disease (BBD) tissues and 5 breast cancer cell lines. All samples were collected from separate patients within the predefined groups. KS1 and BMP3b mRNA expression was quantified by real-time reverse-transcription PCR. Results: The lung cancer cell line A549 which has high levels of RNA expression for these two genes and is not methylated for KS1 or BMP3B was used as a positive control. KS1 was found methylated in 58% of breast cancers, 50% of BBD and 0% of normal breast tissues. The BMP3B gene promoter was methylated in 46% of breast cancers, 5% of BBD and 0% of normal breast tissues. Conclusions: KS1 and BMP3b hypermethylation is a common epigenetic event in breast cancer. KS1 is also methylated in tissue samples from patients with BBD. KS1 may have potential as a marker for early detection/risk prediction of breast cancer in patients with BBD. No significant financial relationships to disclose.