Gene expression profiles of protein kinases and phosphatases obtained by hybridization with cDNA arrays: molecular portrait of human prostate carcinoma

Hybridization with cDNA arrays was used to obtain expression profiles of 263 protein-tyrosine kinase (PTK), protein-tyrosine phosphatase (PTP), dual-specific phosphatase (DuSP), and other genes for the normal prostate tissue, primary prostate carcinomas (PC) of 84 patients, 7 xenografts, and 5 carcinoma cell lines. Analysis of 96 profiles revealed eight clusters of genes coexpressed in PC (coefficient of correlation r > 0.7). According to the known functions of their genes, the clusters were designated as proliferating-cell (CDC42, TOP2A, FGFR3, MYC, etc.), neoangiogenesis and blood-cell (LCK, VAV1, KDR, VEGF, MMP9, SYK, PTPRS, and FLT4), invasion-1 and invasion-2 (ADAM17, TRPM2, DUSP6, VIM, CAV1, CAV2, JAK1, PTPNS1, FYN, and PDGFB), HER2, and PSA/PSM/HER3. Basing on expression profiles of 66 genes, a molecular classification of PC was constructed and allowed discrimination between PC and cell lines or xenografts at 98.9% probability. The results suggested that, along with PSA, PSM (FOLH1), kallikrein-2, and a-2-macroglobulin, cell signaling genes EGFR, HER2, HER3, TOP2, KRT8, KRT18, VEGF, CD44, VIM, CAV1, and CAV2 may serve as diagnostic and prognostic markers in PC. The HER2, VEGF, and CD44 genes and the MMP and ADAM families were assumed to be promising targets for inhibitors of PC cell proliferation and metastasis.     

Oligodontia and its inheritance in Kerry blue terrier

Defects of the premolar tooth formula (oligodontia, tooth number reduction) were studied in dogs of the Kerry blue terrier breed. For this purpose, a database including 480 individuals of 96 litters was constructed. The occurrence of oligodontia was investigated in pedigree groups with inbred and outbred crosses. No selective mating choice for the anomaly under study was found in the sample. The results indicate that oligodontia is inherited, which requires comprehensive study of its genetic control and search for corresponding genes.     

Activation of ras and myc proto-oncogenes in human breast carcinoma and neuroblastoma

DNA from human breast carcinoma (SK-BR-3) and neuroblastoma (LA-N-1) cell lines are capable of inducing foci of transformed NIH 3T3 cells after DNA-mediated gene transfer. The blot hybridization analysis of DNA from primary and secondary NIH 3T3 transformants identified additional sequences homologous to the c-Ha-ras 1 oncogene, and revealed amplification of nucleotide sequences homologous to the v-myc oncogene. Restriction fragments of the amplified myc-related sequences correspond to c-myc (SK-BR-3) and N-myc (LA-N-1) loci of the human genome. The results show that active Ha-ras oncogenes can coexist with altered myc oncogenes in breast carcinomas and neuroblastomas. This suggests that a multi-step mechanism involves both ras and myc genes and their cooperation in the development of these tumors.     

Complex characteristics of the alterations of oncogenes HER-2/ERBB-2, HER-1/ERBB-1, HRAS-1, C-MYC and antioncogenes p53, RB1, as well as deletions of loci of chromosome 17 in colon carcinoma]

Abnormalities of some oncogenes, antioncogenes and losses of heterozygosity (LOH) of chromosome 11p, 17p, and 17q in colorectal carcinomas (CC) was studied. Amplification of ERBB-1/HER-1 oncogene was detected in 2 of 56 cases; ERBB-2/HER-2- in 4 of 62. There was a lack of evidence for C-MYC oncogene amplification (67 cases). LOH of chromosome 11p (HRAS-1 probe) was found in 2 of 37 informative (heterozygous) cases; such events were not accompanied by point mutations in "hot" codons (12th or 61st) in the remaining allele. Prevalence of A3 and A4 alleles of HRAS-1 oncogene (68 cases) as compared to healthy donors was noted. RB-1 (41 cases) and p53 (62 cases) suppressor genes did not show any alterations in Southern-blot analysis. LOH of chromosome 17p (YNZ-22 probe) was found in 15 of 26 heterozygous CC; 17q (THH-59 probe)--in 4 of 16. Analysis of 175th codon of p53 gene revealed only one case of mutation in 35 CC studied. Finally, we were able to detect genetic alterations in 23 of 40 (58%) CC, that were studied on each parameter using Southern-blot. We failed to find any correlation between various molecular abnormalities or clinical characteristics. The data obtained are in disagreement with the view concerning frequent involvement of p53 antioncogene in chromosome 17p deletions.     

Analysis of the genetic structure of the breeding nucleus of the Russian population of purebred Thoroughbred horses at the Extension locus using molecular DNA typing]

Results of the first in Russia survey of the gene pool of the breeding nucleus of the Russian population of thoroughbred horses by means of PCR analysis of the E (Extension) locus MC1R gene mutations are presented. The data on the structure of breeding populations from the leading stud farms Voskhod and Oros with regard to color phenotypes as well as genotype and allele frequencies are presented. The population structure parameters are discussed with respect to possible specific features of microevolution processes.     

Polymorphism of dental formula and segregation of its variants in a pedigree of kerry blue terrier dogs

Polymorphism of the dental formula was analyzed in a sophisticated pedigree of Kerry Blue Terrier. A lack of one or more lower premolars was observed in some dogs. Two different patterns of missing teeth were identified. One pattern consisted in agenesis of a second premolar, often in combination with agenesis of neighbor teeth, including the fourth premolar. In the second pattern, agenesis of a fourth premolar was expressed as an isolated abnormality. It was shown previously that the first pattern is inherited as a recessive trait with near complete penetrance. In this work, the control of a major-gene was demonstrated for the second pattern. This abnormality develops in 70-80% of mutant homozygotes and in no more than 20% of heterozygotes and wild-type homozygotes. It was shown that the two dentition abnormalities are controlled by different genes, which were designated LPA2 and LPA4 (Lower Premolar Agenesis).