Progressive appearance of pigmentation in amelanotic melanoma lesions

We previously described a transgenic mouse line (TG-3) that spontaneously develops pigmented cutaneous melanoma. The generation of several albino mice that developed amelanotic melanoma has also been reported. In this report, we describe an unanticipated result with crosses between C57BL/6-c2j and TG-3 mice. C57BL/6-c2j has the same genetic background as TG-3 (C57BL/6), except for a single base mutation (nucleotide 291) in the tyrosinase locus, resulting in albino coat colour. Only albino F2 mice generated from (TG-3 x C57BL/6-c2j) F1s were selected for further studies. Mice that contained the transgene showed a very high incidence of tumor development as early as 4-6 weeks of age. Raised amelanotic tumors developed on the ear pinnae and perianal region in young F2 albino mice, similar phenotypes as those described earlier for the other albino inbred strains. However, with time, these amelanotic tumors not only increased in size, but unexpectedly developed foci of dark pigmentation. DNA sequence analysis on reverse transcriptase-polymerase chain reactions (RT-PCRs) of tyrosinase mRNA showed that the original tyrosinase mutation was still present in the tumors, indicating that no reversion at this nucleotide had occurred in the tumors. Two different tyrosinase activity assays were used and tyrosinase activity was detected in most tumor samples. Furthermore, Western blot analysis demonstrated various levels of tyrosinase protein in ear tumor samples. These results suggest that tyrosinase and/or melanin are not directly involved in the establishment of melanoma, but that late events occurring within the tumors may generate some tyrosinase activity and production of melanin.