Faculty Bibliography

Summary Background Large congenital melanocytic naevi (LCMN), which develop in utero and are present in approximately one in 20 000 newborns, are associated with markedly increased risks of cutaneous melanoma, leptomeningeal melanoma and neurocutaneous melanocytosis (NCM). Objectives This study examined clinical characteristics associated with melanoma and NCM among patients with LCMN, and estimated the risk of developing melanoma and NCM in these patients. Methods Two hundred and five LCMN patients enrolled in the New York University registry were studied. One hundred and seventy of these patients were followed prospectively. The remaining 35 patients had either melanoma at the time of entry into the registry (n = 6), or had insufficient follow-up information (n = 29). The outcome measures were the occurrence of melanoma and NCM. The associations between these outcomes and the clinical covariates (anatomical location of the LCMN, size of the LCMN, number of satellite lesions, family history of melanoma, patient sex and treatment) were assessed. Results Four of 170 (2.3%) prospectively followed patients developed melanomas, representing a standardized morbidity ratio of 324. Among the entire cohort (n = 205), there were associations between increasing numbers of satellite naevi and the occurrence of melanoma (P = 0.04), and the presence of NCM (P = 0.06). Compared with patients who did not develop these diseases, median LCMN diameters were larger among patients who developed melanoma (49 vs. 39 cm) and NCM (55 vs. 46 cm). Conclusions In LCMN patients, increasing numbers of satellite lesions and larger LCMN diameters are associated with melanoma and NCM

Drosophila germ cell migration is directed by attractive and repulsive guidance cues. We have identified a novel gene, slow as molasses (slam), which is required for germ cell migration. In slam zygotic mutants, germ cells fail to transit off the midgut into the mesoderm. We show that slam is required at this stage in parallel to HMG Coenzyme A reductase, a previously identified germ cell migration gene. Removal of both zygotic and maternal slam results in an earlier defect: a failure to form a cellular blastoderm. Consistent with this phenotype, we found that slam is one of the earliest genes to be transcribed in the embryo, and Slam protein localizes to the growing basal-lateral membrane during blastoderm formation, but Slam is not detected during later stages of embryogenesis. Because slam RNA and protein are expressed earlier than the time when we observe defects in germ cell migration, we propose that Slam is required for the localization of a signal to the basal side of blastoderm cells that is needed later in the posterior midgut to guide germ cells