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Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma.

Charbotel B, Gad S, Caïola D, Béroud C, Fevotte J, Bergeret A, Ferlicot S, Richard S - J Occup Med Toxicol (2007)

Bottom Line: A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups.In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn), at the exon 2 splice site (c.463+1G>C and c.463+2T>C) and within exon 3 (c.506T>C, p.Leu169Pro).No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE.Two patients with a mutation were identified in each group.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMRESTTE, Université Lyon 1, Université de Lyon, Domaine Rockefeller, Lyon, F-69373, France. barbara.charbotel@recherche.univ-lyon1.fr.

ABSTRACT

Background: We investigated the association between exposure to trichloroethylene (TCE) and mutations in the von Hippel-Lindau (VHL) gene and the subsequent risk for renal cell carcinoma (RCC).

Methods: Cases were recruited from a case-control study previously carried out in France that suggested an association between exposures to high levels of TCE and increased risk of RCC. From 87 cases of RCC recruited for the epidemiological study, 69 were included in the present study. All samples were evaluated by a pathologist in order to identify the histological subtype and then be able to focus on clear cell RCC. The majority of the tumour samples were fixed either in formalin or Bouin's solutions. The majority of the tumours were of the clear cell RCC subtype (48 including 2 cystic RCC). Mutation screening of the 3 VHL coding exons was carried out. A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups.

Results: In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn), at the exon 2 splice site (c.463+1G>C and c.463+2T>C) and within exon 3 (c.506T>C, p.Leu169Pro).No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE. Two patients with a mutation were identified in each group.

Conclusion: This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.

No MeSH data available.


Related in: MedlinePlus

Sequence chromatograms of the 4 mutations identified in the VHL gene in this study. R and T are DNA from a commercially available reference and tumour tissue tested respectively. Panels A, B and C correspond to 3 different renal clear cell tumours fixed in formalin solution, whereas panel D corresponds to one of the frozen tumours.
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Figure 1: Sequence chromatograms of the 4 mutations identified in the VHL gene in this study. R and T are DNA from a commercially available reference and tumour tissue tested respectively. Panels A, B and C correspond to 3 different renal clear cell tumours fixed in formalin solution, whereas panel D corresponds to one of the frozen tumours.

Mentions: Mutation screening was performed on the 48 confirmed cases of clear cell RCC, comprising 26 Bouin's fixed tumours, 17 were formalin fixed and 5 frozen tumours. For all of the frozen samples the VHL gene was successfully PCR amplified and sequenced, compared to 71% (12 of 17) of the formalin-fixed samples, and 38% (10 of 26) of the Bouin's fixed tissues. Thus, the VHL gene was entirely sequenced (ie 100% of the coding sequence analysed) for a total of 26 tumours (54%). A VHL mutation was detected in one of the frozen samples at the exon 2 splice site (c.463+1G>C). Furthermore, three VHL mutations were detected in the fixed tumours: one mutation within exon 1 (c.332G>A, p.Ser111Asn), one at the exon 2 splice site (c.463+2T>C), and the last one within exon 3 (c.506T>C, p.Leu169Pro), see Figure 1. These three cases were fixed in formalin solution. No mutations were found in the samples fixed in Bouin's solution. Regarding the codon 81, 75% of the samples (31 fixed and 5 frozen tumours respectively) were successfully sequenced for the corresponding PCR fragment in exon 1 and no mutation at this particular codon was observed.


Trichloroethylene exposure and somatic mutations of the VHL gene in patients with Renal Cell Carcinoma.

Charbotel B, Gad S, Caïola D, Béroud C, Fevotte J, Bergeret A, Ferlicot S, Richard S - J Occup Med Toxicol (2007)

Sequence chromatograms of the 4 mutations identified in the VHL gene in this study. R and T are DNA from a commercially available reference and tumour tissue tested respectively. Panels A, B and C correspond to 3 different renal clear cell tumours fixed in formalin solution, whereas panel D corresponds to one of the frozen tumours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211482&req=5

Figure 1: Sequence chromatograms of the 4 mutations identified in the VHL gene in this study. R and T are DNA from a commercially available reference and tumour tissue tested respectively. Panels A, B and C correspond to 3 different renal clear cell tumours fixed in formalin solution, whereas panel D corresponds to one of the frozen tumours.
Mentions: Mutation screening was performed on the 48 confirmed cases of clear cell RCC, comprising 26 Bouin's fixed tumours, 17 were formalin fixed and 5 frozen tumours. For all of the frozen samples the VHL gene was successfully PCR amplified and sequenced, compared to 71% (12 of 17) of the formalin-fixed samples, and 38% (10 of 26) of the Bouin's fixed tissues. Thus, the VHL gene was entirely sequenced (ie 100% of the coding sequence analysed) for a total of 26 tumours (54%). A VHL mutation was detected in one of the frozen samples at the exon 2 splice site (c.463+1G>C). Furthermore, three VHL mutations were detected in the fixed tumours: one mutation within exon 1 (c.332G>A, p.Ser111Asn), one at the exon 2 splice site (c.463+2T>C), and the last one within exon 3 (c.506T>C, p.Leu169Pro), see Figure 1. These three cases were fixed in formalin solution. No mutations were found in the samples fixed in Bouin's solution. Regarding the codon 81, 75% of the samples (31 fixed and 5 frozen tumours respectively) were successfully sequenced for the corresponding PCR fragment in exon 1 and no mutation at this particular codon was observed.

Bottom Line: A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups.In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn), at the exon 2 splice site (c.463+1G>C and c.463+2T>C) and within exon 3 (c.506T>C, p.Leu169Pro).No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE.Two patients with a mutation were identified in each group.

View Article: PubMed Central - HTML - PubMed

Affiliation: UMRESTTE, Université Lyon 1, Université de Lyon, Domaine Rockefeller, Lyon, F-69373, France. barbara.charbotel@recherche.univ-lyon1.fr.

ABSTRACT

Background: We investigated the association between exposure to trichloroethylene (TCE) and mutations in the von Hippel-Lindau (VHL) gene and the subsequent risk for renal cell carcinoma (RCC).

Methods: Cases were recruited from a case-control study previously carried out in France that suggested an association between exposures to high levels of TCE and increased risk of RCC. From 87 cases of RCC recruited for the epidemiological study, 69 were included in the present study. All samples were evaluated by a pathologist in order to identify the histological subtype and then be able to focus on clear cell RCC. The majority of the tumour samples were fixed either in formalin or Bouin's solutions. The majority of the tumours were of the clear cell RCC subtype (48 including 2 cystic RCC). Mutation screening of the 3 VHL coding exons was carried out. A descriptive analysis was performed to compare exposed and non exposed cases of clear cell RCC in terms of prevalence of mutations in both groups.

Results: In the 48 cases of RCC, four VHL mutations were detected: within exon 1 (c.332G>A, p.Ser111Asn), at the exon 2 splice site (c.463+1G>C and c.463+2T>C) and within exon 3 (c.506T>C, p.Leu169Pro).No difference was observed regarding the frequency of mutations in exposed versus unexposed groups: among the clear cell RCC, 25 had been exposed to TCE and 23 had no history of occupational exposure to TCE. Two patients with a mutation were identified in each group.

Conclusion: This study does not confirm the association between the number and type of VHL gene mutations and exposure to TCE previously described.

No MeSH data available.


Related in: MedlinePlus