Biomedical subjects

I Laurendeau

Publications and source records attributed to I Laurendeau.

21 records · Page 2Linked to original sources

PubMed1998

Clonal analysis of macronodules in cirrhosis.

Several arguments suggest that most hepatocellular carcinomas (HCCs) occurring in human cirrhotic livers arise from large hepatocellular nodules or macronodules. Except for nodules with obvious features of HCC, there exist no consistent criteria enabling the differentiation between benign regenerative and neoplastic, potentially malignant macronodules. Surrogate markers able to accurately discriminate those lesions that will evolve toward a HCC are required. In this study, we investigated the clonality of 26 macronodules isolated from eight cases of explanted cirrhotic livers in women by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each macronodule, a large set of pathological features was evaluated and used to classify the macronodules into four groups: entirely benign-looking nodule (type 1), low-grade dysplastic nodule (type 2), high-grade dysplastic nodule (type 3), and HCC (type 4). Clonal analysis showed that 14 macronodules (54%) were monoclonal and 12 (46%) were polyclonal. Monoclonality was detected in 5 of 11 (45%) nodules from groups of entirely benign-looking and low-grade dysplastic nodules (types 1 and 2) and in 9 of 15 (60%) nodules from the group of high-grade dysplastic nodule and HCC (types 3 and 4). Neither the etiology of cirrhosis nor the size or histological classification of macronodules was correlated with the clonal status. In conclusion, clonal analysis of macronodules enables the differentiation between mono- and polyclonal macronodules in cirrhosis. Because monoclonal macronodules are prone to evolve to HCC, the determination of the clonal status of a macronodule could provide additional information for evaluating the prognosis of these lesions.

Adult↗

PubMed1998

Clonal analysis of renal sporadic angiomyolipomas.

Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.

Adult↗

PubMedDate not supplied

Human TIP49b/RUVBL2 gene: genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3.

Bacterial DNA helicase RuvB protein is an essential component in homologous recombination and DNA double-strand break repair. Here, we report the gene structure of TIP49b/RUVBL2, a second putative human homologue of the bacterial RuvB gene. This gene contains 15 exons and 14 introns. The TIP49b/RUVBL2 open reading frame encodes a protein of 463 amino acids, showing 43% identity with the RUVBL1 protein. The TIP49b/RUVBL2 gene is physically linked to the human CGB/LHB gene cluster on chromosome 19q13.3. Genomic sequence analysis revealed that the TIP49b/RUVBL2 gene is very close (55 nucleotides in length) to the LHB gene, in the opposite orientation. The very close co-location of the mouse homologues of the human TIP49b/RUVBL2 and LHB genes was also conserved on mouse chromosome 7. Co-ordinated transcriptional regulation between the TIP49b/RUVBL2 and LHB genes was not observed. TIP49b/RUVBL2, like RUVBL1, was expressed ubiquitously in all human tissues examined and more strongly in testis. As TIP49b/RUVBL2 is expected to be involved in recombination repair and is located in a chromosome region frequently amplified in breast cancer, we quantified TIP49b/RUVBL2 gene expression by using real-time quantitative RT-PCR in a series of breast tumour samples. None of the tumour samples showed an altered TIP49b/RUVBL2 transcription level relative to normal breast tissue.

ATPases Associated with Diverse Cellular Activitie↗