Evidence by molecular profiling for a placental origin of infantile hemangioma

Abstract

The origin of the pathogenic endothelial cells in common infantile hemangioma is unknown. We show here that the transcriptomes of human placenta and infantile hemangioma are sufficiently similar to suggest a placental origin for this tumor, expanding on recent immunophenotypical studies that have suggested this possibility [North, P. E., et al. (2001) Arch. Dermatol. 137, 559-570]. The transcriptomes of placenta, hemangioma, and eight normal and diseased tissues were compared by hierarchical and nonhierarchical clustering analysis of >7,800 genes. We found that the level of transcriptome similarity between placenta and hemangioma exceeded that of any other tissue compared and paralleled that observed between a given tissue and its derived tumor, such as normal and cancerous lung. The degree of similarity was even greater when a subset of endothelial cell-specific genes was analyzed. Genes preferentially expressed in both placenta and hemangiomas were identified, including 17-beta hydroxysteroid dehydrogenase type 2 and tissue factor pathway inhibitor 2. These data demonstrate the value of global molecular profiling of tissues as a tool for hypothesis-driven research. Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium.

Fig. 1.

High similarity between hemangioma and placental transcriptomes. (a) Hierarchical clustering of 7,815 genes in the “sample dimension.” (b) Self-organizing maps visualized with gedi. Each tile within a mosaic represents a minicluster of genes (≈10 on average) with similar expression patterns across all samples. Tile's color indicates minicluster's average gene expression level. Samples are from: B, brain; H, hemangioma; P, placenta; S, skin; M, muscle; L, lung; Sc, scleroderma; Sq, squamous lung; SmC, small cell lung; Car, carcinoid lung.

Fig. 2.

Hierarchical clustering of a 29 EC-associated gene subset, demonstrating high similarity in placental and hemangioma endothelium.

Fig. 3.

Pearson correlation coefficient of a 29 EC-associated gene subset (a and b) or 29 random genes (c) (1,000 permutations). (a) Color map, with pairwise comparisons in each square. (b and c) Average of r for same-pairwise comparisons, arranged in decreasing order: green (same-tissue pairs), orange (different-tissue pairs), black with arrow (H-P). Abbreviations are as in Fig. 1.