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M Santibanez-Koref

Publications and source records attributed to M Santibanez-Koref.

12 recordsLinked to original sources
PubMed1995

A radiation hybrid panel for human chromosome 6q.

A panel of 63 radiation-reduced hybrids has been derived from a mouse cell line containing a neo-marked human Chromosome (Chr) 6, primarily to provide a resource for higher resolution localization of new markers. Hybrids were generated with radiation doses of 40-400 Gy, selected in G418, and were shown by PCR to contain the neo gene. PCR was also used to score the retention of 15 loci that map from 6q13 to q25.2 of the current consensus map, plus six other loci assigned to 6q26-q27. An average retention frequency of 27.8% was observed, with the highest frequencies at D6S313 and D6S280 (63.5%) located near the centromere at 6q13, and at D6S283 (68.5%) at 6q16.3-q21, presumably close to the neo integration site. Lowest frequencies (4.8%) were observed for telomeric markers. All markers segregated independently except D6S297 and D6S193. Agreement and some improvement to the current consensus map of 6q was made by mapping 12 loci by the non-parametric statistical method of Falk. In addition, deletion mapping with informative hybrids allowed the ordering of six loci from 6q26 to q27 and permitted some integration of maps of this region.

Animals↗
PubMed1995

Allelic imbalance of chromosome 6q in ovarian tumours.

Previous work has implicated putative tumour-suppressor (ts) genes at 6q27 and a broad region at 6p12-q23. Here we report the results of a coded, randomised study of allelic imbalance at 12 loci on 6q on 40 pairs of coded tumour-blood pairs from patients with ovarian tumours. Our results provide clear evidence for the involvement of different regions of 6q in tumours of different histological subtypes. The involvement in serous tumours of a ts gene at the distal site is confirmed. However, proximal 6q presents a complex picture, with possibly three further ts genes: one at 6q21-23.3 involved at high frequency in benign and endometrioid tumours, another at 6q14-q15, also involved in endometrioid tumours, and a third suggested by a smallest region of deletion at 6q16.3-q21, between D6S275 and D6S300, that appears to be involved in early stage tumours. These observations point the way to a statistical study of the involvement of 6q in tumours of different histological type and staging performed on larger cohorts of samples.

Adenocarcinoma, Mucinous↗
PubMed1995

Proximal 6q, a region showing allele loss in primary breast cancer.

To define regions of deletion of chromosome 6q in breast cancer, we scored 18 (CA)n microsatellites for allelic imbalance (AI) in 42 paired blood/tumour samples. Heterozygosity frequencies of the markers in the sample population ranged from 31% to 92% (mean 68%). Two regions of the chromosome arm showed AI values greater than the background range of 10-22% (mean 17%) of informative cases that was observed with five markers spanning 6q21-q25.2. Firstly, seven markers gave AI values that averaged 35% in a region flanked by D6S313 (AI = 10%) at 6q13 and D6S283 (AI = 17%) at 6q16.3-21. The second region showed marginally increased AI at 6q25.2-q27 and included D6S193, previously shown to be close to a tumour-suppressor gene involved in ovarian carcinoma. Since AI of 6q in breast cancer was shown previously to be due predominantly to loss of heterozygosity, our results suggest the presence of at least two tumour-suppressor genes on 6q that are involved in breast cancer. The proximal region has not been recognised in breast cancer before and is involved in a higher frequency of tumours than the distal region.

Alleles↗
PubMed1994

Physical mapping of 43 STSs to human chromosome 6.

We have localized 43 sequence-tagged sites by deletion mapping using a chromosome 6 panel of 18 translocation hybrids. Thirty-four loci were mapped to the long arm of chromosome 6, and 9 were mapped to 6p. Many of the loci contain (CA)n dinucleotide repeated sequences and therefore will be useful markers for mapping genes on chromosome 6.

Alleles↗
PubMed1994

Deletion of a common region on the long arm of chromosome 6 in acute lymphoblastic leukaemia.

We have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6P1 at 6q14-15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor gene within this interval.

Adolescent↗
PubMed1994

Common region of deletion on the long arm of chromosome 6 in non-Hodgkin's lymphoma and acute lymphoblastic leukaemia.

We have used fluorescence in situ hybridisation (FISH) with a series of yeast artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q) to define the region(s) of deletion in seven cases of non-Hodgkin's lymphoma (NHL), in which a deletion of 6q had been detected by conventional cytogenetics. The FISH analysis detected two regions of deletion: (i) A proximal region flanked by M6P1 (6q14-15) and FYN (6q21), containing D6S246, which was missing in all seven cases. This locus was also found to be deleted in all six cases of acute lymphoblastic leukaemia (ALL) studied previously. (ii) A second region of 6q, which was distal to 6q23.1 (D6S238) and included ESR (6q25.1) and D6S281 (6q27), which was shown to be present in all our cases of ALL, was found to be deleted in 4 of the 7 cases of NHL. Our results support the suggestion that tumour suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be present within these regions.

Adult↗
PubMed1993

An immediate early human gene encodes an Id-like helix-loop-helix protein and is regulated by protein kinase C activation in diverse cell types.

Transcription factors characterized by the presence of a helix-loop-helix (HLH) domain play a central role in the regulation of cell growth/differentiation and tumorigenesis. We report here the cDNA sequence of a human early-response gene, designated HLH 1R21, encoding a 15-kDa HLH protein that lacks a basic, DNA-binding domain and which by a number of criteria appears to be the human homologue of mouse HLH 462. Like its murine counterpart, HLH 1R21 protein functions as an Id (inhibitor of DNA binding) transcription factor by inhibiting the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer oligonucleotide in vitro. However HLH 1R21 does not inhibit the binding of HLH Max protein to a Max-binding oligonucleotide in vitro, indicating that it has limited promiscuity in its ability to antagonize the function of other HLH transcription factors. In addition, HLH 1R21 mRNA transcripts are regulated by phorbol ester treatment of a diverse range of human cell lines and, when overexpressed in mouse NIH3T3 cells, HLH 1R21 induces a morphologically transformed phenotype.

3T3 Cells↗
PubMed1992

Isolation and partial characterization of murine O6-alkylguanine-DNA-alkyltransferase: comparative sequence and structural properties.

A cDNA encoding murine O6-alkylguanine-DNA-alkyltransferase (ATase) has been sequenced after isolation from total liver RNA by the polymerase chain reaction using oligonucleotide primers derived from the rat ATase cDNA sequence. Functionally active murine ATase protein has been expressed in Escherichia coli at high levels (about 2% of total protein) and purified to apparent homogeneity (molecular mass 26 kDa). In liquid hybridization experiments, anti-human ATase polyclonal antibodies inhibited human but not rat or mouse ATase, whereas anti-rat polyclonal antibodies inhibited rat and mouse but not human ATase. Both antibodies detected all mammalian ATases tested by western analysis so far. These results indicate some common epitopes and at least one unique human epitope. We compared the amino-acid sequence of the murine ATase with those of other mammalian and bacterial ATases. The proteins of this family all have a large domain (approximately 70 amino acids) of highly conserved residues flanking the sequence PCHRV, which contains the alkyl-accepting cysteine residue of the active site. No evidence was found in the sequences for helix-turn-helix, leucine-zipper, or zinc-finger motifs for DNA recognition and binding. Nuclear localization signals (basic-residue-rich regions) could not be uniquely identified in the mammalian members of the family. Outside of the conserved PCHRV region, there were major differences between prokaryotic and eukaryotic proteins at the primary structure level: there was a series of proline-rich motifs, but these also varied between sequences.

Amino Acid Sequence↗
PubMedDate not supplied

Avoidance of DNA methylation. A virus-encoded methylase inhibitor and evidence for counterselection of methylase recognition sites in viral genomes.

The ocr+ gene of bacterial virus T7 codes for the first protein recognized to inhibit a specific group of DNA methylases. The recognition sequences of several other DNA methylases, not susceptible to Ocr inhibition, are significantly suppressed in the virus genome. The bacterial virus T3 encodes an Ado-Met hydrolase, destroying the methyl donor and causing T3 DNA to be totally unmethylated. These observations could stimulate analogous investigations into the regulation of DNA methylation patterns of eukaryotic viruses and cells. For instance, an underrepresentation of methylation sites (5'-CG) is also true for animal DNA viruses. Moreover, we were able to disclose some novel properties of DNA restriction-modification enzymes concerning the protection of DNA recognition sequences in which only one strand can be methylated (e.g., type III enzyme EcoP15) and the primary resistance of (unmethylated) DNA recognition sites towards type II restriction endonuclease EcoRII.

Base Sequence↗