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An immunoglobulin G (IgG) preparation of the serum from a patient with active Graves' disease was used to isolate cDNA clones from a lambda gt11 cDNA library of human thyroid follicular carcinoma tissue by immunoscreening. One of these clones, hML-7, is further characterized herein by sequencing, Northern analysis, and chromosomal mapping. The clone reacted with IgG preparations from the sera of 14 of 19 patients with active Graves' disease but not with IgG preparations from 11 normal individuals, three patients with toxic thyroid adenoma, and three with rheumatoid arthritis. The hML-7 cDNA hybridized to a 3.6 kilobase (kb) mRNA transcript in poly(A+) RNA preparations from human thyroid tissue and continuously cultured rat thyroid cells; expression of this transcript in rat FRTL-5 thyroid cells was positively regulated by TSH. The 3.6 kb transcript was less abundant in rat liver (BRL3A) cells or differentiated rat (L6) myoblasts than in cultured rat thyroid cells and was not detectable in mouse L-M fibroblasts, human IM-9 lymphocytes, Chinese hamster ovary cells, or human cervical carcinoma cells. The cDNA from hML-7 was sequenced and compared with the sequence of cross-hybridizing cDNA clones isolated from human Graves' thyroid and rat FRTL-5 thyroid cell lambda gt11 expression libraries. A 1.05 kb open reading frame, which is highly conserved between human and rat, was defined. The predicted amino acid sequence of 348 residues exhibited a strong homology with the mitochondrial ADP/ATP carrier protein (adenine nucleotide translocase; ADP/ATP translocator) and with two other members of the same mitochondrial protein family, the phosphate carrier and the hydrogen ion uncoupling protein. The gene represented by the hML-7 cDNA has been assigned to human chromosome 10.

Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.

Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the beta peptide of brain amyloid from Alzheimer's disease. The open reading frame of the sequenced clone coded for 97 amino acids, including the known amino acid sequence of this polypeptide. The 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus. The gene is highly conserved in evolution and has been mapped to human chromosome 21.