Altered expression and deletion of RMO1 in osteosarcoma.

In order to increase our understanding of the molecular events underlying osteosarcoma progression, the expression of approximately 950 genes was examined in 24 primary and metastatic osteosarcoma tumor specimens. A gene, RMO1, was isolated with decreased expression in metastatic samples. Real-Time PCR corroborated this pattern, revealing lower expression in the primary sample in 6 of 7 cases for which both primary and metastatic osteosarcoma samples were available from the same patient (p = 0.034). RMO1 is located at 2q33, a region of frequent loss of heterozygosity in cancer, and exhibited loss of heterozygosity in 6 out of 9 primary osteosarcoma tumor samples (67%). Loss of heterozygosity is evident in primary tumors while the decrease in gene expression is seen in the metastatic samples, indicating that these 2 events are separately implicated in cancer progression. Cloning of RMO1 revealed an open reading frame with multiple splice forms with significant homology to GRB7, 10 and 14 and MIG10 in the region containing a Pleckstrin homology domain and a Ras association domain, suggestive of a role in cell signaling and migration. Northern blot analysis indicated that RMO1 mRNA is ubiquitously expressed in tissues except for peripheral blood leukocytes. These data suggest that RMO1 may be a candidate for a protein involved in inhibiting tumor progression. 2004 Wiley-Liss, Inc.