In the accounting for about all cancer deaths with deaths in estimated

The development of wide-genome approaches such as highdensity single nucleotide polymorphism -arrays, has further improved the sensitivity of aCGH and provided the opportunity for large scale genotyping with a more accurate definition of the magnitude of the abnormalities detected, through the identification of copy number variation and loss of heterozigosity for hundreds of thousands of SNPs . This allows highly precise mapping of those genetic changes occurring across the entire genome in a major fraction of all tumor cells, providing a promising starting point for the identification of novel candidate genes affected by such genomic alterations and profiles. To the best of our knowledge, only Jones et al and Harada et al have previously applied the SNP-array technology to primary PDAC samples and none of them has investigated so far the potential association between SNP-array profiles of copy number alterations and tumor histopathology. In the present study, we applied higher density 500 K SNP arrays with a 2.5 Kb of resolution, to a series of 20 PDAC tumors vs. paired peripheral blood samples from an identical number of BKM120 PI3K inhibitor patients who underwent complete tumor resection. Our major goal was to map the most common reccurrent chromosomal alterations present at diagnosis in PDAC tumors and correlate them with the histopathological subtypes of the disease. Overall, the copy number values obtained confirm that primary PDAC frequently carry extensive gains of chromosomes 1q, 7q, 8q and 20q, together with PD 0332991 company losses of chromosomes 1p, 9p, 12q, 17p and 18q; these chromosomal regions, contain multiple cancer genes known to be directly related to PDAC disease. Most interestingly, we show for the first time the existence of two major groups of PDAC defined on the basis of the altered SNP-array profiles which showed a close association with tumor histopathology. Tissue specimens were obtained at diagnosis from 20 sporadic PDAC patients -mean age of 67 years -. All patients underwent surgical tumor resection at the Division of Hepatobiliary and Pancreatic Surgery of the University Hospital of Salamanca , between October 2003 and October 2008. The study was approved by the local ethics committee of the University Hospital of Salamanca and written informed consent was given by each individual prior to entering the study, according to the Helsinki Declaration.

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