WHAT'S KNOWN ON THIS SUBJECT: The incidence of childhood and adolescent melanoma has been significantly increasing up to 2004. Risk factors (fair skin, light-colored hair/eyes, female gender, presence of nevi, family history, increased number of sunburns, and exposure to UV radiation) are associated with melanoma.WHAT THIS STUDY ADDS: This study describes incidence trends of melanoma diagnosed between the ages of 0 and 19 years and from 1973 through 2009 by gender, stage and age at diagnosis, primary site, and exposure to UV radiation. abstract OBJECTIVE: Childhood and adolescent melanoma is rare but has been increasing. To gain insight into possible reasons underlying this observation, we analyzed trends in melanoma incidence diagnosed between the ages of 0 and 19 years among US whites by gender, stage, age at diagnosis, and primary site. We also investigated incidence trends by UV-B exposure levels.METHODS: By using Surveillance, Epidemiology, and End Results (SEER) program data (1973-2009), we calculated age-adjusted incidence rates (IRs), annual percent changes, and 95% confidence intervals for each category of interest. Incidence trends were also evaluated by using joinpoint and local regression models. SEER registries were categorized with respect to low or high UV-B radiation exposure. RESULTS:From 1973 through 2009, 1230 children of white race were diagnosed with malignant melanoma. Overall, pediatric melanoma increased by an average of 2% per year (95% confidence interval, 1.4%-2.7%). Girls, 15-to 19-year-olds, and individuals with low UV-B exposure had significantly higher IRs than boys, younger children, and those living in SEER registries categorized as high UV-B. Over the study period, boys experienced increased IRs for melanoma on the face and trunk, and females on the lower limbs and hip. The only decreased incidence trend we observed was among 15-to 19-yearolds in the high UV-B exposure group from 1985 through 2009. Local regression curves indicated similar patterns.CONCLUSIONS: These results may help elucidate possible risk factors for adolescent melanoma, but additional individual-level studies will be necessary to determine the reasons for increasing incidence trends.

A B S T R A C T PurposeHereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks. Patients and MethodsIn a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale. ResultsNearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) -containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age Ͻ 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age Ն 1 year (HR, 1.75; 95% CI, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P ϭ .01). ConclusionThis comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb.

Our previous studies have argued persuasively that in murine sarcoma virus ts110 (MuSVts110) the gag and mos genes are fused out of frame due to a-1.5-kilobase (kb) deletion of wild-type murine sarcoma virus 349 (MuSV-349) viral information. As a consequence of this deletion, infected cells grown at 39°C appear morphologically normal, producing a 4-kb viral RNA and a truncated gag gene product, P58gag. At 33°C, however, MuSVtsllO-infected cells appear transformed, producing two viral RNAs, about 4 and 3.5 kb in length, and two viral proteins, P58gag and P85gag-mos. Recent SI nuclease analyses (Nash et al., J. Virol. 50:478-488, 1984) suggested strongly that at 33°C about 430 bases surrounding the out-of-frame gag-mos junction and bounded by consensus splice donor and acceptor sites are excised from the 4-kb RNA to form the 3.5-kb RNA. As a result of this apparent splicing event, the gag and mos genes seemed to be fused in frame and allowed the translation of P85gag-ms. In the present study, DNA primers hybridizing to the MuSVts11O 4-anid 3.5-kb RNAs just downstream of the gag-mos junction points were used to sequence these junctions by the primer extension method. We observed that, relative to wild-type MuSV-349 5.2-kb RNA, the MuSVtsll0 4-kb RNA had suffered a 1,488-base deletion as a result of the fusion of wild-type gag gene nucleotide 2404 to wild-type mos gene nucleotide 3892. This gag-mos junction is out of frame, containing both TAG and TGA termination codons in the reading frame 42 and 50 bases downstream of the gag-mos junction, respectively. Thus, the MuSVts110 4-kb RNA can only be translated into a truncated gag precursor containing an additional C-terminal 14 amino acid residues derived from an alternate mos gene reading frame. Similar analyses of the MuSVtsllO 3.5-kb RNA showed a further loss of both gag and mos sequences over those deleted in the original 1,488-base deletion. In the MuSVtsllO 3.5-kb RNA, we found that gag nucleotide 2017 was fused to mos nucleotide 3936 (nucleotide 2449 in the MuSVtsllO 4-kb genome). This 431-base excised fragment is bounded exactly by in-frame consensus splice donor and acceptor sequences. As a consequence of this splice event, the TAG codon is excised and the restoration of the original mos gene reading frame allows the TGA codon to be bypassed. As a complement to the above sequence data, blot hybridization studies showed unequivocally that MuSVtsll0-infected nonproducer 6m2 cells contain a single, approximately 4.4-kb MuSVtsll0-related viral genome. The restriction map of this provirus was consistent with a relationship to wild-type MuSV-349 viral DNA by way of a 1.5-kb deletion between the gag and mos genes. No 3.5-kb provirus could be detected in 6m2 cells, necessitating that the 3.5-kb RNA be derived from the transcription product of the 4.4-kb genome. In MuSVtsllO producer 206-21C cells chronically superinfected with Moloney murine leukemia virus, however, an integrated 3.9-kb MuSVtsll0-related genome was readily apparent. From its restriction map, this 206-2...

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