Loss of heterozygosity in malignant melanoma at loci on chromosome 11 and 17 implicated in the pathogenesis of other cancers.

Forty-six cases of sporadic melanoma have been investigated for loss of heterozygosity at 4 loci: D11S29 (11q23), YNZ22 (17p13.3), TP53 (17p13.1); and NM23 (17q22). Each of the loci is thought to be important in the pathogenesis of other tumours. Mutations were found infrequently at the YNZ22, NM23, and TP53 loci. At D11S29, however, the frequency of mutation in the melanoma samples was high (67%) and mutations at this locus were associated with younger age at presentation. This region of chromosome 11 is also commonly mutated in breast cancers and haematological malignancies. Genetic aberrations at D11S29 may therefore represent nonspecific mutations found in several malignancies or part of a pathway common to the malignant phenotype.

Structure of the human aldose reductase gene.

The structure and sequence of the human gene for aldose reductase (AR) was determined by analysis of cDNA and genomic clones. The AR gene was independently isolated from two different cosmid libraries and the clones were characterized by restriction mapping, Southern blotting, and DNA sequencing. The gene extends over approximately 18 kilobases and consists of 10 exons giving rise to a 1,384 nucleotide mRNA (excluding the poly(A) tail). The human aldose reductase gene codes for a 316-amino acid protein with a molecular mass of 35,858 daltons. The size range for the exons is 82-168 base pairs (bp), whereas that for the introns is 325 to about 7,160 bp. A major site of transcription initiation in liver was mapped to an A residue 31 nucleotides upstream from the A of the ATG initiation codon. The promotor region of the gene contains a TATA (TATTTA) box and a CCAAT box which are located 37 and 104 nucleotides upstream, respectively, from the transcription initiation site. We have found four Alu elements in the AR gene; two are found in intron 1 and one each in intron 4 and intron 9.