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

The pathogenesis of congenital cystic adenomatoid malformation (CCAM) is unknown and its natural history is unpredictable. Fatty acid binding protein-7 (FABP-7) has been previously described in brain and breast development, but never before in the lung. We investigate gene expression in CCAM, and hypothesize that CCAM results from an aberration in the signaling pathway during lung development. Under IRB approval, tissue specimens of 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 <0.05. Validation of differential expression was achieved at the RNA and protein levels. FABP-7 was underexpressed in fetal CCAM compared with fetal lung in both the microarray and by RT-PCR. Findings were duplicated by Western Blot analysis and immunohistochemistry. This is the first description of FABP-7 in the human lung. Decreased expression of FABP-7 in fetal CCAM compared with normal fetal lung at both the RNA and protein levels suggests FABP-7 may have a role in pulmonary development and in the pathogenesis of CCAM.