HIC1 promoter methylation and 17p13.3 allelic loss in invasive ductal carcinoma of the breast

Parrella, Paola; Scintu, Marina; Prencipe, Maria; Poeta, Maria Luana; Gallo, Antonietta Pia; Rabitti, Carla; Rinaldi, Monica; Tommasi, Stefania; Paradiso, Angelo; Schittulli, Francesco; Valori, Vanna Maria; Toma, Salvatore; Altomare, Vittorio; Fazio, Vito Michele

doi:10.1016/j.canlet.2004.08.026

Next »Cancer Letters
Volume 222, Issue 1 , Pages 75-81, 10 May 2005

HIC1 promoter methylation and 17p13.3 allelic loss in invasive ductal carcinoma of the breast

Paola Parrella
- Laboratory of Gene Therapy and Oncology, IRCCS, ‘Casa Sollievo della Sofferenza’, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
- Corresponding author. Tel.: +39 0882 416262; fax: +39 0882 416260.
Marina Scintu
- Laboratory of Gene Therapy and Oncology, IRCCS, ‘Casa Sollievo della Sofferenza’, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
Maria Prencipe
- Laboratory of Gene Therapy and Oncology, IRCCS, ‘Casa Sollievo della Sofferenza’, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
Maria Luana Poeta
- CIR Section of Molecular Medicine and Biotechnology, ‘Campus BioMedico University’, Rome, Italy
Antonietta Pia Gallo
- Laboratory of Gene Therapy and Oncology, IRCCS, ‘Casa Sollievo della Sofferenza’, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
Carla Rabitti
- Department of Pathology, ‘Campus BioMedico University’, Rome, Italy
Monica Rinaldi
- Neurobiology and Molecular Medicine Institute, CNR, Rome, Italy
Stefania Tommasi
- Clinical Experimental Oncology Laboratory, and Department ‘Donna’, National Cancer Institute, Bari, Italy
Angelo Paradiso
- Clinical Experimental Oncology Laboratory, and Department ‘Donna’, National Cancer Institute, Bari, Italy
Francesco Schittulli
- Clinical Experimental Oncology Laboratory, and Department ‘Donna’, National Cancer Institute, Bari, Italy
Vanna Maria Valori
- Department of Onco-Hematology IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo (FG), Italy
Salvatore Toma
- Department of Onco-Hematology IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo (FG), Italy
Vittorio Altomare
- Breast Unit, Department of Surgery, ‘Campus BioMedico University’, Rome, Italy
Vito Michele Fazio
- Laboratory of Gene Therapy and Oncology, IRCCS, ‘Casa Sollievo della Sofferenza’, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
- CIR Section of Molecular Medicine and Biotechnology, ‘Campus BioMedico University’, Rome, Italy

Received 6 July 2004; received in revised form 25 August 2004; accepted 27 August 2004.

Abstract

The HIC1 gene is a transcriptional regulator commonly methylated in a variety of human cancer. Thirty-three invasive ductal carcinomas of the breast and 21 matched normal breast tissues were analysed for HIC1 promoter methylation, and allelic loss of a 700kb region spanning the gene locus. At least one genetic or epigenetic abnormality was found in 27 of the carcinomas tested (82%). Promoter methylation was demonstrated in 21 carcinomas (64%), and nine normal tissues (43%), whereas 18 malignant tumors (54%) showed allelic loss. Concomitant loss of heterozigosity and promoter hypermethylation in the region spanning HIC1 was detected in eight carcinomas (24%) suggesting that in this subset of tumors both copies of the gene are functionally lost. These observations support a role for the HIC1 gene in the pathogenesis of breast ductal carcinomas.