genetic analysis of congenital cystic adenomatoid malformation reveals a novel pulmonary gene: fatty...

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Genetic analysis of congenital cystic adenomatoid malformation reveals a novel pulmonary gene: Fatty acid binding protein-7 (brain type) AmyWagner, MD, Amber Stumbaugh, MS, Zachary Tigue, BS, Edmondson Jess, BS, Agnes Paquet, MS, Diana Farmer, MD, FACS, Samuel Hawgood, MD University of California, San Francisco; Virginia Mason Medical Center, Seattle, WA INTRODUCTION: The pathogenesis of congenital cystic adenoma- toid malformation (CCAM) is unknown and its natural history is unpredictable. Fatty acid binding protein-7 (FABP-7) has been de- scribed in brain and breast development, but not in the lung. We investigate gene expression in CCAMs versus control lung tissue, and hypothesize CCAM is a result of an aberration in the signaling path- way during lung development. METHODS: Under IRB approval, tissue specimens of four groups (fetal CCAM, fetal control, postnatal CCAM, and postnatal control) were examined and microarray analysis was performed. Candidate differentially expressed genes were selected with log-odds ratio (B) 0 and False Discovery Rate (FDR) at 0.05. Validation of differential expression was achieved at the RNA and protein levels. RESULTS: FABP-7 was under-expressed in fetal CCAM compared to fetal lung. RT-PCR of FABP-7 expression in fetal CCAM was also under- expressed compared to control, by a 12-fold difference. These findings were duplicated by Western Blot analysis and immunohisto-chemistry. CONCLUSIONS: This is the first description of FABP-7 in the hu- man lung. Decreased expression of FABP-7 in fetal CCAM com- pared to normal fetal lung at both the RNA and protein levels sug- gests FABP-7 may have a role in pulmonary development and in the pathogenesis of CCAM. S39 Vol. 205, No. 3S, September 2007 Surgical Forum Abstracts

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Page 1: Genetic analysis of congenital cystic adenomatoid malformation reveals a novel pulmonary gene: Fatty acid binding protein-7 (brain type)

Genetic analysis of congenital cystic adenomatoidmalformation reveals a novel pulmonary gene: Fattyacid binding protein-7 (brain type)Amy Wagner, MD, Amber Stumbaugh, MS, Zachary Tigue, BS,Edmondson Jess, BS, Agnes Paquet, MS, Diana Farmer, MD, FACS,Samuel Hawgood, MDUniversity of California, San Francisco; Virginia Mason MedicalCenter, Seattle, WA

INTRODUCTION: The pathogenesis of congenital cystic adenoma-toid malformation (CCAM) is unknown and its natural history isunpredictable. Fatty acid binding protein-7 (FABP-7) has been de-scribed in brain and breast development, but not in the lung. Weinvestigate gene expression in CCAMs versus control lung tissue, andhypothesize CCAM is a result of an aberration in the signaling path-way during lung development.

METHODS: Under IRB approval, tissue specimens of four groups(fetal CCAM, fetal control, postnatal CCAM, and postnatal control)were examined and microarray analysis was performed. Candidatedifferentially expressed genes were selected with log-odds ratio (B) �0 and False Discovery Rate (FDR) at 0.05. Validation of differentialexpression was achieved at the RNA and protein levels.

RESULTS: FABP-7 was under-expressed in fetal CCAM compared tofetal lung. RT-PCR of FABP-7 expression in fetal CCAM was also under-expressed compared to control, by a 12-fold difference.These findings wereduplicated by Western Blot analysis and immunohisto-chemistry.

CONCLUSIONS: This is the first description of FABP-7 in the hu-man lung. Decreased expression of FABP-7 in fetal CCAM com-pared to normal fetal lung at both the RNA and protein levels sug-gests FABP-7 may have a role in pulmonary development and in thepathogenesis of CCAM.

S39Vol. 205, No. 3S, September 2007 Surgical Forum Abstracts