Loss of the PRKAR1A Gene Locus Identified by Conventional Cytogenetic and Fluorescence In Situ Hybridization Analysis in Solitary Superficial Angiomyxoma.
Rachael E Neff, Yuanyuan Zhang, Dali Huang, Xiao-qiong Liu, Julia A Bridge. University of Nebraska Medical Center, Omaha
Background: Superficial angiomyxoma is a distinct but often poorly recognized benign cutaneous neoplasm. Superficial angiomyxoma most frequently arises sporadically, but it may also occur as a feature of the autosomal dominant disorder Carney complex (CNC). PRKAR1A is a tumor suppressor gene on chromosome 17 that is mutated in some Carney complex (CNC) patients. Superficial angiomyxoma has not previously been subjected to cytogenetic or molecular cytogenetic analysis.
Design: Conventional cytogenetic analysis was performed on a representative portion of a solitary superficial angiomyxoma arising on the thigh of a 54 year old male. In addition, a 192 kb bacterial artificial chromosome (BAC RP11-120M18) clone identified as spanning the PRKAR1A (17q24) locus was fluorescently labeled to conduct higher resolution analysis. After establishing the specificity of the probe and coupling it with a CEP 17 copy number control probe, dual color FISH studies were performed to assess the PRKAR1A copy number on destained metaphase cells and FFPE tissue sections of the cytogenetically analyzed superficial angiomyxoma as well as FFPE tissue sections on one additional superficial angiomyxoma, two cases of cutaneous focal mucinosis and one negative control.
Results: The following abnormal chromosomal complement was detected in the 54 year old male's superficial angiomyxoma: 46,XY,ins(17;17)(q25;q12q21). FISH studies revealed homozygous loss of the PRKAR1A locus in the cytogenetically analyzed superficial angiomyxoma. The remaining cases were negative for PRKAR1A loss by FISH. A mutational mechanism other than deletion such as a submicroscopic mutation resulting in a truncated or inactive protein may be responsible for PRKAR1A inactivation in the single case of FISH negative sporadic superficial angiomyxoma.
Conclusions: The role of germline PRKAR1A mutations in CNC, to include the presence of superficial angiomyxomas, is well recognized. The data from the current study showing homozygous loss of the PRKAR1A locus in one non-CNC superficial angiomyxoma supports a somatic role of the PRKAR1A tumor suppressor gene in sporadic superficial angiomyxoma as well.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 123, Wednesday Afternoon