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B Martínez-Delgado

Publications and source records attributed to B Martínez-Delgado.

13 recordsLinked to original sources
PubMed2006

A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers.

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2-associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97-147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16-bp insertion and the variant allele for the Arg72Pro (No Ins-72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins-72Pro haplotype (OR: 2.69; 95% CI: 1.15-6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype.

Adult↗
PubMed2005

Differential expression of NF-kappaB pathway genes among peripheral T-cell lymphomas.

Nuclear factor kappa B (NF-kappaB) is one important pathway in T-cell proliferation and survival. In a previously reported microarray study, we found NF-kappaB pathway genes differentially expressed between peripheral (PTCL) and lymphoblastic lymphomas. Here, we investigated the expression of NF-kappaB pathway genes using cDNA microarrays in a group of 62 PTCL and in reactive lymph nodes. We found two different subgroups of PTCL based on the expression of NF-kappaB pathway genes. One-third of PTCL showed clearly reduced expression of NF-kappaB genes, while the other group was characterized by high expression of these genes. This distinction was found among all T-cell lymphoma categories analyzed (PTCL unspecified, angioimmunoblastic, cutaneous and natural killer/T lymphomas) with the exception of anaplastic lymphomas (ALCL), which were characterized by reduced NF-kappaB expression in anaplastic cells. Quantitative RT-PCR and immunohistochemical analysis of NF-kappaB-p65 protein confirmed these differences among PTCL subgroups. Importantly, we found that differentiation between NF-kappaB-positive and -negative PTCL could be of clinical interest. The expression profile associated to reduced expression of NF-kappaB genes was significantly associated with shorter survival of patients and seems to be an independent prognostic factor in a multivariate analysis.

Adult↗
PubMed2003

Characterization of the A673 cell line (Ewing tumor) by molecular cytogenetic techniques.

The A673 cell line was established from a patient with a primary rhabdomyosarcoma (RMS), which is referred to in the literature either as a Ewing tumor (ET) or as RMS. Although the two tumoral types are associated with specific and well-characterized translocations, no cytogenetic report on this cell line has been published. We characterized the A673 cell line using a combination of spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase chain reaction (RT-PCR), which revealed the presence of a complex karyotype and a translocation involving chromosomes 11 and 22 and the fusion of EWS and FLI1 genes, both events being specific to ET. Neither cytogenetics nor molecular alterations specific to RMS were found.

Chromosome Aberrations↗
PubMed2002

Complex cytogenetic abnormalities including telomeric associations and MEN1 mutation in a pediatric ependymoma.

Ependymomas are neuroectodermal tumors of the brain and spinal cord. Some recurrent cytogenetic aberrations have been reported in these tumors, including alterations involving chromosomes 22, 6, and 11. However, consistent molecular alterations have not been identified in ependymal tumors. We studied a recurrent ependymoma in a 3-year-old patient by standard cytogenetic and molecular analysis of TP53 and MEN1 genes. In the present case, we found many of the cytogenetic features previously described as being recurrent in ependymomas, including unstable telomeric alterations. Furthermore, we detected a novel acquired heterozygous mutation in the MEN1 gene. The chromosomal instability produced by the telomeric alterations and the mutation in the MEN1 gene could be important events in the tumorigenesis of ependymomas.

Base Sequence↗
PubMed2001

IgH, TCR-gamma, and TCR-beta gene rearrangement in 80 B- and T-cell non-Hodgkin's lymphomas: study of the association between proliferation and the so-called "aberrant" patterns.

The current study analyzes the rearrangement pattern of immunoglobulin H (IgH), T-cell receptor (TCR)-gamma, and TCR-beta genes in a group of 80 non-Hodgkin's lymphomas (NHL) of different histologic subtypes (43 B-cell and 37 T-cell types). The sensitivity and specificity provided by polymerase chain reaction amplification of these loci are evaluated. The association between the proliferation index and the presence of the so-called "aberrant" or "dual" rearrangements is also considered. Ninety-one percent of B-cell NHL showed IgH gene monoclonality, and 21% also exhibited a monoclonal pattern in one of the TCR genes. Among T-cell NHL, the sensitivity of the study was 65% for the TCR-gamma gene and 46% for the TCR-beta gene. The total sensitivity was 76%, amplifying both loci. IgH gene aberrant rearrangements were observed in 16% of T-cell neoplasms. A substantial percentage of dual rearrangements were detected in precursor and mature B- and T-cell NHL. B-cell NHL showed a tendency toward higher values of proliferation when aberrant rearrangements were present; however, this trend was not significant. Furthermore, in the case of T-cell NHL there was a significant negative association between these two variables.

Antigens, Nuclear↗
PubMed2001

Multiplex-polymerase chain reaction assay for the detection of prognostically significant translocations in acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: The presence of specific chromosomal translocations in acute lymphoblastic leukemias (ALL) plays an important role in determining the prognosis of the patients. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent translocations in ALL: t(9;22), t(1;19), t(4;11), t(12;21). DESIGN AND METHODS: Our approach uses a multiplex-polymerase chain reaction (PCR) method, which involves two rounds of PCR using fluorescence-labeled nested primers. The chimeric transcripts resulting from these translocations can be identified by agarose gel electrophoresis or by fluorescence analysis. To validate this method we carried out the analysis in 42 pediatric ALL samples previously studied by cytogenetic and fluorescent in situ hybridization (FISH) techniques. RESULTS: In all samples with a known translocation detected by cytogenetic or FISH techniques, the same translocation was identified by the multiplex-PCR assay. Moreover, with this method we detected rearrangements in five patients in clinical remission and in two patients at diagnosis for whom karyotypes were normal and rearrangements had not been detected. The application of this multiplex-PCR assay was also useful in cases without cytogenetic results. INTERPRETATION AND CONCLUSIONS: These results show that the multiplex-PCR method allows reliable, sensitive and rapid detection of the prognostically significant translocations in ALL. We believe that this assay combined with cytogenetic analysis should be the strategy of choice for the initial diagnostic phase of acute lymphoblastic leukemia, and that it could be used not only at diagnosis but also to follow-up these alterations in remission samples without previous controls.

Child↗
PubMed2000

Identification by comparative genomic hybridization of genetic changes involved in tumoral progression of a T-cell non-Hodgkin lymphoma.

Comparative genomic hybridization (CGH) was used to detect chromosomal imbalances in tumor DNA from two relapsed samples obtained in stages II and IV of a T-cell non-Hodgkin lymphoma in order to identify genetic mechanisms involved in tumor progression of this neoplasm. With conventional cytogenetic techniques (CCT), a complex hyperdiploid karyotype was obtained in stage IV. Using CGH analysis, a normal profile was observed in stage II, whereas gains of 6p11.2, 7q11.2, 7q21-->q32, 7q34, 10p13, Xp11.4, and loss of 4q33-->qter chromosomal regions were detected in stage IV.

Humans↗
PubMed1999

Genetic and clinical analysis in 10 Spanish patients with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610 amino acid named menin whose function is unknown. We have studied 10 unrelated MEN 1 kindreds by a complete sequencing analysis of the entire gene; mutations were identified in nine of them: five deletions, one insertion, two nonsense mutation and a complex alteration consisting of a deletion and an insertion that can be explained by a hairpin loop model. Two of the mutations have been previously described; the other seven were novel, and they were scattered throughout the coding sequence of the gene. As in previous series, no correlation was found between phenotype and genotype.

Base Sequence↗
PubMed1999

[MLL rearrangements in acute leukemias].

PURPOSE: In present study we have studied MLL rearrangements in a serie of acute myeloid, lymphoblastic and biphenotypic leukaemias. PATIENTS AND METHODS: We analyzed a total of 11 cases: 9 acute myeloid leukaemias (M4 and M5 subtypes in FAB classification), 1 lymphoid leukaemia, and 1 acute biphenotypic leukaemia. We studied bone marrow samples from all patients by using conventional cytogenetic techniques and fluorescence in situ hybridization (FISH) with an MLL probe. We also analyzed the correlation between clinical features and genetic results. RESULTS: Cells from 6 patients showed to contain MLL rearrangements and these arose in all types of leukaemias included in this study. Some MLL rearrangements were detected by FISH in kariotypically normal cases or without cytogenetic evidence of 11q23 aberration. MLL gene duplication has been observed in two cases with M4 and biphenotypic leukaemia, respectively. The presence of MLL gene rearrangements does not shape a group of patients with a common clinical pattern. CONCLUSIONS: MLL rearrangements occurs in a wide variety of leukemias. These rearrangements should be screened by FISH techniques, taking into account that gene duplications could arise in cases with normal karyotype. MLL rearrangements appear to have a considerable clinicopathologic heterogeneity.

Adult↗
PubMed1998

[Application of modified comparative genomic hybridization in the genetic analysis of 5 lymphoid neoplasms].

To analyze the utility of performing modified comparative genomic hybridization (mCGH) as a complementary technique to conventional cytogenetic techniques in the genetic analysis of lymphoid neoplasms. Modified comparative genomic hybridization and subsequent FISH techniques were performed in 5 lymphoid neoplasms cases diagnosed in Fundación Jiménez Díaz. The latter was done in order to confirm the results obtained with mCGH. Gains of chromosomal regions not detected with conventional cytogenetic techniques were detected by mCGH. A good correlation in the results obtained between conventional cytogenetic and mCGH techniques was observed. Nevertheless, mCGH enables the detection and subsequent identification of gains of genetic sequences undetectable with cytogenetic techniques with possible diagnostic and prognostic value.

Chromosomes, Human, Pair 10↗
PubMed1995

[Characterization of mutation of the P53 gene in lymphomas].

PURPOSE: To analyze P53 mutations in a series of NHL and to determine its implication in the inactivation of the tumor suppressor function. MATERIAL AND METHODS: We analyzed 18 lymphomas by SSCP (exons 5 to 9) and subsequent sequencing technics to detect and characterize mutations on this gene. Loss of heterozigosity (LOH) was also studied with a VNTR near the p53 gene and with a intragenic microsatellite, comparing tumor and normal tissue. RESULTS: We found altered bands by SSCP in 5 cases, 4 of them have been described by sequencing analysis. One case was a polymorphism and the others were missense mutations. All mutations appeared in high grade lymphomas. Only one case showed LOH in both VNTR and microsatellite. CONCLUSIONS: This results suggest that p53 mutations may be associated with more malignant lymphomas.

Base Sequence↗
PubMedDate not supplied

[Identification of a de novo mutation in a patient without von Hippel-Lindau syndrome: clinical and diagnostic implications].

Von Hippel-Lindau (VHL) disease is characterized by a high predisposition to develop retinal angiomas, hemangioblastomas of the central nervous systems, renal cysts and renal carcinomas, pheochromocytomas, pancreatic cysts, and cystadenomas of the epididymis. The VHL gene was isolated in 1993; this fact allows to carry out presymptomatic diagnostic of this disease. We report on the case of patient with the suspicious++ and of hereditary VHL, although she had not familial history. By means of sequence the VHL gene was studied a mutation in exon 2 (GTT130CTT) that results in an amino acid change was found. This mutation could not be detected in her parents, pointing out that this is a de novo case. Patient has two sons, of 18 and 13 years old. The genetic analysis of the youngest showed that he was not a mutation carrier; while the eldest denied to be explored. The genetic study allows, in cases without familial history, to determine if they have the hereditary form of the disease and to study the siblings periodically until the beginning of the disease.

Adult↗