[319] Analysis of PRKAR1A Gene Locus in Sporadic Cardiac Myxomas.

Stanley Radio, Yuanyuan Zhang, Dali Huang, Rachael Neff, Julia Bridge. University of Nebraska Medical Center, Omaha

Background: Cardiac myxoma most frequently arises sporadically, but it may also occur as a feature of the autosomal dominant disorder Carney complex syndrome (CCS). Mutations of the tumor suppressor gene PRKAR1A represent an underlying cause of CCS which includes myxomas in multiple sites, spotty pigmentation and endocrine overactivity. Cytogenetic studies of cardiac myxoma are rare, but to date 17q23-24, the chromosomal locus of PRKAR1A, has not been shown to be karyotypically rearranged. To the best of our knowledge, molecular cytogenetic studies for the examination of submicroscopic or cryptic anomalies have not yet been conducted.
Design: Five cases of histologically confirmed cardiac myxoma with paraffin blocks available were identified from the files of the Cardiovascular Registry at UNMC. Conventional cytogenetic analysis was performed on one of these from a 71 year old male. Selection and labeling of a 192 kb bacterial artificial chromosome ( BAC RP11-120M18) clone designed to span the PRKAR1A (17q23-24) locus was carried out for higher resolution analysis. After establishing the specificity of the probe and coupling it with a copy number control probe (CEP 17), dual color FISH studies were performed to assess the PRKAR1A copy number on representative paraffin-embedded tissue sections from the cytogenetically analyzed cardiac myxoma as well as 4 other cardiac myxomas (2Males, 2 Females, mean age 68 ) and one negative control.
Results: A hypodiploid clone with loss of chromosomes 21 and 22 accompanied by the presence of telomeric associations involving chromosome 16 and various partner chromosomes was identified in 16 cells of the karyotypically analyzed myxoma. FISH studies revealed homozygous loss of the PRKAR1A locus in one myxoma from a 74 year old female. The other 4 were negative for loss by FISH.
Conclusions: Deletion or loss of the PRKAR1A locus is demonstrated in a case of sporadic cardiac myxoma, supporting a tumor suppressor role for this gene in non-CCS associated cardiac myxomas.
Category: Cardiovascular

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 26, Wednesday Afternoon


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