Biomedical subjects

Martine Muleris

Publications and source records attributed to Martine Muleris.

6 recordsLinked to original sources

PubMed2006

Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma.

In a large-scale analysis of gene expression in pancreatic cancer, we isolated the homologue of the mouse Rab20. The mouse protein was previously identified during a search for novel Rab proteins, a family of small GTP-binding proteins involved in the regulation of intracellular vesicular transport. The Rab20 protein has no close relationship to any member of the Rab protein subfamily. In contrast to other members, it contains an insertion of 40 amino acids of unknown function and an inversion of 3 amino acids at the position corresponding to codon 61 in p21ras proteins. Using immunofluorescence and immunoelectron microscopy, we localized the Rab20 protein in the vicinity of the Golgi apparatus. Rab20 expression was detected by Western blot analysis in 11 of 11 pancreatic tumor cell lines and 7 of 8 primary pancreatic carcinomas. Absent or very faint expression was observed in normal pancreas cell extracts. Immunohistochemical analysis of Rab20 in tissues showed low or absent expression in normal pancreas and stronger expression in 15 of 18 exocrine pancreatic adenocarcinomas. Rab20 was also detected in preneoplastic pancreatic intraductal neoplasia lesions, suggesting that its up-regulation may be an early event in pancreatic carcinogenesis.

Adenocarcinoma↗

PubMed2005

Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites.

Various studies suggest a tight relationship between chromosome rearrangements driving tumor progression and breaks at loci called common fragile sites. Most of these sites are induced after perturbation of the replication dynamics, notably by aphidicolin treatment. We have mapped the majority of these sites to the interface of R and G bands, which calls into question the previous assignment of aphidicolin-sensitive sites to R bands. This observation suggests that most of them correspond to loci that ensure the transition between early and late replicating domains. We show that calyculin A, which triggers chromosome condensation at any phase of the cell cycle but does not markedly impair replication, induces damage in the chromosomes of human lymphocytes treated in G(2) but not in G(1) phase. We demonstrate that these lesions colocalize with those induced by aphidicolin treatment. Hence, common fragile site stability is compromised, whether aphidicolin delays replication or calyculin A advances condensation. We also show that, in cells that go through an unperturbed S phase, completion of their replication and/or replication-associated chromatin reorganization occur all along the G(2) phase, which may explain their inability to condense properly after calyculin A treatment during this phase of the cell cycle.

Aphidicolin↗

PubMed2005

Ductal breast carcinoma develops through different patterns of chromosomal evolution.

In a previous study that used comparative genomic hybridization (CGH) to analyze 43 ductal breast carcinomas selected for hyperdiploidy, we proposed the existence of two distinct pathways of chromosomal evolution. In the present study, in which we reassessed our cytogenetic findings on 158 ductal breast carcinomas selected for having a modal number of chromosomes of fewer than 60, we confirmed the existence of two subtypes of tumors. Along with the great majority of tumors (142 of 158) that evolved through structural rearrangements with no or very few whole-chromosome gains, we found that a minor subset (16 of 158) evolved through progressive gains of whole chromosomes with no or only a few associated rearrangements. In this article, we describe the karyotypes of these 16 tumors together with data from CGH, which was performed for 10 of them. Chromosomes 5, 7, 8, and 20 were the most frequently gained. Our findings support the evidence of a new pathway of chromosomal evolution in a small subset of ductal breast carcinomas characterized by numerical chromosome aberrations.

Aged↗

PubMed2005

Ductal breast carcinomas with whole chromosome gains as a particular subset of near-diploid tumors with different metastasis free survival.

We recently proposed the existence of a subtype of slightly hyperdiploid ductal breast cancers with cytogenetic alterations differing from those usually observed in the majority of these tumors. We aimed to establish whether these tumors, which represent about 50% of those with a DNA index (DI) comprised between 1.1 and 1.3, correspond to a particular clinicopathological entity. A retrospective study of 1771 patients operated for ductal carcinomas was performed. Three classes of tumors constituted according to DI were compared for the usual clinicopathological factors and clinical outcome. About 690 tumors (39%) were diploid/hypodiploid (DI < 1.1), 134 (7.6%) were hyperdiploid (1.1 < or = DI < 1.3) and 947 (53.4%) were polyploid (DI > or = 1.3). Median follow-up time was 106 months (range 1-177). Polyploid tumors were significantly associated with large tumor size, advanced clinical stage, high histological grade and S-phase fraction (SPF), positive lymph nodes and loss of steroid receptors. Hyperdiploid and diploid/hypodiploid tumors were similar for all the variables except SPF which was significantly higher in hyperdiploid tumors (p < 0.001). Overall survival was similar in hyperdiploid and diploid/hypodiploid tumors in univariate and multivariate analysis, while hyperdiploid tumors were significantly related to a poorer metastasis free survival, both in univariate (p = 0.023) and multivariate analysis (p = 0.031). Despite very close initial clinicopathological and biological characteristics, hyperdiploid tumors differed from diploid/hypodiploid tumors by a higher risk of metastasis, possibly related to their increased SPF.

Aneuploidy↗

PubMed2004

Characterization of a new cytogenetic subtype of ductal breast carcinomas.

About 50% of ductal breast carcinomas do not yield analysable karyotypes after short-term culturing. Comparison of the cytogenetic subset to the whole data set of tumors revealed that slightly hyperdiploid tumors, that is, with DNA index between 1.05 and 1.3, were under-represented in tumors for which cytogenetic analysis was successful. The purpose of this study was to determine whether the pattern of chromosome imbalances in this subset differs from that generally reported. Comparative genomic hybridization (CGH) was used on 43 primary ductal breast carcinomas selected for slight hyperdiploidy. Microsatellite instability (MSI), TP53 mutation and expression were also investigated. All tumors were MSI negative. In all, 18 tumors (42%) presented mostly unbalanced chromosome rearrangements and DNA amplifications, with only few or no whole chromosome gains (WCG). This pattern of chromosome imbalances corresponds to that described in most breast tumors by previous cytogenetic and CGH analyses. It was associated with TP53 mutation in 17% of tumors. Another subset of 17 tumors (39%) displayed different and new features, characterized by recurrent gains of whole chromosomes 5, 7 and 8 with few chromosome rearrangements, rare DNA amplifications and no TP53 mutation. Eight tumors with as many rearrangements as WCG were left unclassified. We propose that, beside a major pathway characterized by multiple chromosome rearrangements, there is a minor pathway mainly characterized by WCG.

Adult↗

PubMed2002

Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas.

We have identified a novel human cDNA overexpressed in a colon carcinoma cell line, TC7, established from a tumor with a normal karyotype arising in a patient with a hereditary nonpolyposis colorectal carcinoma. The OCC-1 (overexpressed in colon carcinoma-1) gene is composed of six exons and located in the q24.1 region of chromosome 12. It is transcribed as two mRNA species that differ in their 5'- and 3'-terminal ends. Abundant accumulation of both transcripts was found in placenta, skeletal muscle, kidney, and pancreas tissues. Absent or very faint expression was observed in heart, brain, lung and liver tissues. Overexpressed in colon carcinoma-1 cDNA direct in vitro translation of several polypeptides whose size is shorter than 9 kDa. Attempts to produce antibodies against these synthesized polypeptides in Escherichia coli failed. The absence of sequences at the mRNA and DNA levels hybridizing with mouse sequences together with the absence of a large open reading frame raise the possibility that OCC-1 sequences appeared recently in evolution and are transcribed as two noncoding regulatory RNA. Elevated levels of OCC-1 mRNA were observed in three of eight colon carcinomas as compared to normal mucosa of the same patient. Since these tumors shared the same characteristics of having a near diploid karyotype, OCC-1 overexpression may be a hallmark of this subset of colon carcinomas.

Adult↗