Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

Parris, Toshima Z,1978Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Oncology (author)

Genetic and epigenetic (DNA methylation, histone modifications, microRNA expression) crosstalk promotes inactivation of tumor suppressor genes or activation of oncogenes by gene loss/hypermethylation or duplications/hypomethylation, respectively. The 8p11-p12 chromosomal region is a hotspot for genomic aberrations (chromosomal rearrangements, amplifications and deletions) in several cancer forms, including breast carcinoma where amplification has been associated with increased proliferation rates and reduced patient survival. Here, an integrative genomics screen (DNA copy number, transcriptional and DNA methylation profiling) performed in 229 primary invasive breast carcinomas identified substantial coamplification of the 8p11-p12 genomic region and the MYC oncogene (8q24.21), as well as aberrant methylation and transcriptional patterns for several genes spanning the 8q12.1-q24.22 genomic region (ENPP2, FABP5, IMPAD1, NDRG1, PLEKHF2, RRM2B, SQLE, TAF2, TATDN1, TRPS1, VPS13B). Taken together, our findings suggest that MYC activity and aberrant DNA methylation may also have a pivotal role in the aggressive tumor phenotype frequently observed in breast carcinomas harboring 8p11-p12 regional amplification.

Kovács, Anikó,1961 (author)
Hajizadeh, Shahin,1966 (author)
Nemes, Szilard,1977Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xnemsz (author)
Semaan, MayGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology (author)
Levin, Max,1969Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xlevma (author)
Karlsson, Per,1963Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xkperd (author)
Helou, Khalil,1966Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xhelkh (author)
Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för onkologi (creator_code:org_t)

By the author/editor: Parris, Toshima ...; Kovács, Anikó, 1 ...; Hajizadeh, Shahi ...; Nemes, Szilard, ...; Semaan, May; Levin, Max, 1969; show more...; Karlsson, Per, 1 ...; Helou, Khalil, 1 ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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