Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Identification of two novel isoforms of the ZNF162 gene: a growing family of signal transduction and activator of RNA proteins.

By differential screening of a cDNA library obtained from a GM-CSF-dependent human myeloid leukemia cell line (GF-D8), we identified two novel isoforms of the recently described ZNF162 gene, which is apparently linked to multiple endocrine neoplasia type 1. The shorter of these new isoforms, called B3, presents an open reading frame (ORF) of 1713 bp coding for 571 amino acids. Its nucleotide sequence is homologous to the cDNA coding for the ABCDF isoform of ZNF162, except for a 4-nucleotide insertion that results in a frame shift of the ORF starting from nucleotide 1725 of the ZNF162 sequence. As a consequence, the predicted translation product of B3 contains the consensus sequence of the A motif (G-X-X-X-X-G-K-S) of the "ATP/ GTP binding site," which is characteristic of several protein families including protein kinases. Moreover, B3 shows the use of a different stop codon and contains a different tyrosine-rich COOH terminus. The longer isoform, called B4, differs from the ABCDEF isoform of ZNF162 by the insertion, at position 2137, of 383 nucleotides leading to a different, proline-rich COOH terminus. The complex transcription pattern of the ZNF162 gene is characterized by four transcripts, of approximately 3.9, 3.7, 3.2, and 2.9 kb, in GF-D8 cells. The 3.7- and 2.9-kb transcripts are expressed in resting GF-D8 cells. Upon stimulation with GM-CSF the expression of these mRNAs is up-regulated in parallel with the induction of two additional transcripts of 3.9 and 3.2 kb. The same pattern of expression has also been observed in freshly isolated myeloid leukemia cells and normal CD34+ stem cells. In light of these data, and since GM-CSF is known to stimulate signal transduction pathways, it becomes relevant that all the different isoforms of ZNF162 contain the KH module, which is a sequence motif present in proteins playing a major role in regulating cellular RNA metabolism. A search for functional domains demonstrates that ZNF162 belongs to a new and growing family of genes dubbed STAR (signal transduction and activator of RNA) proteins that are thought to play a downstream role in cell signaling and also in RNA binding. The mammalian members include Sam68, which is a target of Src, Fyn, and Grb2, and the newly cloned mouse quaking proteins (qkI) necessary in early embryogenesis and myelination. Moreover, since ZNF162 is highly conserved from yeast to humans, it implies that this new pathway has a significant function.