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Catherine Gallou

Publications and source records attributed to Catherine Gallou.

5 recordsLinked to original sources
PubMed2004

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.

Adult↗
PubMed2002

Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma.

A mechanism decreasing oxidative metabolism during normal cell division and growth is expected to direct substrates toward biosyntheses rather than toward complete oxidation to CO(2). Hence, any event decreasing oxidative phosphorylations (OXPHOS) could provide a proliferating advantage to a transformed or tumor cell in an oxidative tissue. To test this hypothesis, we studied mitochondrial enzymes, DNA and OXPHOS protein content in three types of renal tumors from 25 patients. Renal cell carcinomas (RCCs) of clear cell type (CCRCCs) originate from the proximal tubule and are most aggressive. Chromophilic RCCs, from similar proximal origin, are less aggressive. The benign renal oncocytomas originate from collecting duct cells. Mitochondrial enzyme and DNA contents in all tumor types or grades differed significantly from normal tissue. Mitochondrial impairment increased from the less aggressive to the most aggressive RCCs, and correlated with a considerably decreased content of OXPHOS complexes (complexes II, III, and IV of the respiratory chain, and ATPase/ATP synthase) rather than to the mitochondrial content (citrate synthase and mitochondrial (mt)DNA). In benign oncocytoma, some mitochondrial parameters (mtDNA, citrate synthase, and complex IV) were increased 4- to 7-fold, and some were slightly increased by a factor of 2 (complex V) or close to normal (complexes II and III). A low content of complex V protein was found in all CCRCC and chromophilic tumors studied. However F(1)-ATPase activity was not consistently decreased and its impairment was associated with increased aggressiveness in CCRCCs. Immunodetection of free F(1)-sector of complex V demonstrated a disturbed assembly/stability of complex V in several CCRCC and chromophilic tumors. All results are in agreement with the hypothesis that a decreased OXPHOS capacity favors faster growth or increased invasiveness.

Base Sequence↗
PubMedDate not supplied

Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors.

Medullary carcinoma is a poorly differentiated breast cancer with a high histologic grade and a paradoxically good prognosis. It accounts for only 3 percent of all breast cancers except in BRCA-1 families, in which it can account for as many as 13 percent of cancers. To date, only histologic criteria have been used to define this tumor type. In an attempt to more clearly define the genetic pathway leading to this subtype of cancer, we recently demonstrated that nearly 100 percent of these carcinomas display p53 mutations. In the present study, we extended our analysis to include HIN-1, a candidate tumor suppressor that has been shown to be silenced by methylation in the majority of breast tumors. In striking contrast to unselected sporadic invasive ductal carcinoma, we show that medullary carcinomas do not display a high frequency of HIN-1 methylation (p less than 0.001). This feature is also found in BRCA-1 associated tumors that shared several histologic characteristics with medullary carcinomas of the breast. Medullary carcinoma of the breast should therefore be considered to be a unique entity defined by specific histologic and molecular traits.

Breast Neoplasms↗
PubMedDate not supplied

Delineation of a 2.8 megabases region harboring a potential tumor suppressor gene involved in renal cell carcinoma, that is commonly deleted from chromosome 14.

MATERIALS AND METHODS: To investigate the genetic alterations that occur during the development of renal cell carcinomas (RCC), we used 20 microsatellite markers to examine 48 renal cell carcinomas for allelic losses of chromosome arm 14q. RESULTS: We identified 14q LOH in 31% of cases. Twelve tumors were entirely lacking the 14q arm and three were partially deleted. For the first time on fresh tumors, these findings led to the delineation of a 17.9 Mb region between markers D14S281 and D14S277 that is commonly deleted. Interestingly, this segment overlaps with the previously reported 37.8 Mb commonly deleted region. CONCLUSION: Taken together these results allowed us to define a new 2.8 Mb segment between markers D14S588 and D14S277 that potentially harbors a tumor suppressor gene involved in the development of RCC which can be reached by positional cloning.

Adult↗