[938] Utility of Whole-Genome SNP Microarrays in Renal Tumors: Diagnostic Implications

Selene Koo, Agata Minor, Poluru Reddy, Loren Joseph, Carrie Fitzpatrick, Tatjana Antic, Maria Tretiakova. University of Chicago, Chicago, IL

Background: Conventional cytogenetics has provided a useful adjunct to traditional morphological categorization of renal cell carcinomas (RCC), particularly in histologically ambiguous cases, as the various subtypes have characteristic chromosomal abnormalities. More recently, single nucleotide polymorphism (SNP) microarrays have been shown to complement karyotyping with whole-genome copy number data at high resolution and copy number-neutral loss of heterozygosity (LOH). Few studies have investigated RCC cases with equivocal histology, instead focusing on the common RCC subtypes. In this study, we use SNP microarrays to investigate the genetic profiles of RCCs with conventional and ambiguous morphologies.
Design: Genomic DNA was isolated from twelve fresh frozen RCC specimens and a case of oncocytosis, and processed according to the standard protocol for Affymetrix Genome-Wide Human SNP Array 6.0. Acquired data were analyzed using the Affymetrix Chromosome Analysis Suite.
Results: LOH and copy number analysis data are summarized in the table.

Tumor typeChromosomal alterations consistent with published SNP microarray dataNovel chromosomal alterations
Clear cell (n=4)+1q, +2p, +2, -3p, LOH 4q, +5q, +7q, +8q, +12q, LOH 16p, +16p, LOH 16q, +16, LOH 18q+1p, -4q, -4, -5q, -8p, -9q, +10p, +10q, -13, -14q, +18q, +20, -21q
Chromophobe (n=2)-1, -1p, -2, -6, -10, -13, -17, -20q, -21-2q, -3, -9
Papillary (n=3)+3, +7, +12, +16, +17, +21+1q, LOH 3, LOH 8q, -11q, -18, +20, -22, -Y
Oncocytosis (n=1)-1+7, -Y
TFE3 (n=2)No abnormalities
Clear cell papillary (n=1)No abnormalities
Bold: identified in all cases; italic: classic alterations

Three cases with ambiguous morphology were reclassified as a result of this analysis. One case that was originally diagnosed as conventional clear cell RCC was reclassified as TFE3 translocation-associated RCC on the basis of normal copy number data and confirmed by TFE3 immunohistochemical stain. The classification of two other morphologically overlapping cases were changed between clear cell RCC and clear cell papillary RCC based on 3p loss and no chromosomal alterations, respectively.
Conclusions: SNP microarrays provide a powerful tool for analyzing genetic abnormalities in RCCs and aid in proper classification of RCC cases with ambiguous morphology. The results led to the reclassification of three out of twelve cases, which has both treatment and prognostic implications. Our data confirm and expand the scope of genetic abnormalities found in the subtypes of RCC, and facilitate understanding the molecular basis for these cancers.
Category: Genitourinary (including renal tumors)

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 137, Monday Morning


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