Affymetrix Arrays Used to Identify Gene Amplified Associated with Breast Cancer

Study conducted by researchers at King Faisal Specialist Hospital and Research centre in the Kingdom of Saudi Arabia and University Medical Centre Hamburg

Researchers at the King Faisal Specialist Hospital and Research Centre (KFSH & RC) in the Kingdom of Saudi Arabia and University Medical Centre Hamburg (UMCH) have used affymetrix microarray technology to discover a gene amplification associated with breast disease and breast cancer. The study, "Estrogen receptor alpha (ESRI) gene amplification id frequent in breast cancer." was published in a recent issue of Nature Genetics.

"We introduced Affymetrix Genechip(R) technology in the kingdom of Saudi Arabia four years ago to help bridge the gap between laboratory findings and clinical application," said Khawla AlKuraya, M.D., F.C.A.P., a leading cancer researcher at KFSH & RC. "Since then we have been able to investigate the etiology of a variety of tumors of different lineages to develop diagnostics or therapeutic strategies. Our overall goal is to improve the management of cancer in the Kingdom of Saudi Arabia and provide unprecedented tools for translational research throughout the region."

Dr. Khawla's research team at the KFSH &RC and the research team at UMCH used the Affymetrix Genechip (R) Human Mapping Arrays to identify and measure copy number variations found in the breast cancer. The team found that 99 percent of tumors with ESR1 amplification showed estrogen reception protein over expression, compared with 66.6 percent of cancer without ESR1 amplpification.ESR1 amplification might be instrumental in defining a subtype of primary breast cancers and perhaps other proliferate breast diseases that have particularly high estrogen receptor expressions.

"Since then, we have been able to investigate the etiology of a variety of tumors of different lineages to develop diagnostic or therapeutic strategies. Our overall goal is to improve the management of cancer in the Kingdom of Saudi Arabia and provide unprecedented tools for translational research throughout the region."

Dr. Khawla's research team at KFSH & RC and the research team at UMCH used the Affymetrix Gene Chip(R) Human Mapping Arrays to identify and measure copy number variations found in breast cancer. The team found that 99 percent of tumors with ESR1 amplification showed estrogen receptor protein over expression, compared with 66.6 percent of cancers without ESR1 amplification. ESR1 amplification might be instrumental in defining a subtype of primary breast cancers and perhaps other proliferate breast diseases that have particularly high estrogen receptor expression.>

"King Faisal Specialist Hospital and Research Centre is the largest and most influential research institute in the Middle East, and we are very pleased to say that this paper in Nature Genetics is the first major scientific publication authored by a customer in the Persian Gulf region," said Robert Wells, vice president of corporate affairs and international markets at Affymetrix. "The team at KFSH & RC and University Medical Center Hamburg is part of a growing list of Affymetrix customers from around the world who are helping to accelerate cancer research."

Abstract of a new research paper by Khawla Al-Kuraya, Department of Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and King Fahad National Center for Children's Cancer & Research, Riyadh, Saudi Arabia.

In an attempt to find genes that may be of importance in malignant progression of papillary thyroid carcinoma (PTC) in the Middle East, which therefore can be targeted in cancer therapy, we screened and validated the global gene expression in PTC using cDNA expression arrays and immunehistochemistry (IHC) on tumor tissue microarrays. Twenty-nine PTC tissue specimens were compared with seven non-cancerous thyroid specimens by use of cDNA microarray. Results for selected genes were confirmed by quantitative real-time PCR. Protein expression of selected genes was further studied using a tissue microarray consisting of 536 PTCs and compared with histological non-cancerous tissue samples.

One hundred and ninety-six genes were over expressed in PTC tissues relative to non-cancerous thyroid tissues. The genes that were up-regulated in PTC were involved in cell cycle regulation, cell signaling, and oncogenesis. Among these genes, c-MET was identified by immunohistochemical methods as a protein that is over expressed in 37% of PTCs and was significantly associated with more aggressive behavior, eg higher stage, nodal involvement, and tall cell variant (p value = 0.01, 0.01 and 0.04, respectively). In this study, 55% of the PTC cases expressed activated AKT (P-AKT), which suggests that activated AKT may play an important role in PTC tumourigenesis. The fact that most of the PTC cases that had activated AKT showed over expression of c-MET (p=0.027) leads us to hypothesize that c-MET may be an alternative mechanism of AKT activation in Middle Eastern PTCs. Finally, our data suggest that c-MET dysregulation is associated with aggressive behavior and may serve as a molecular biomarker and potential therapeutic target in this disease.