Dataset Information

Aristolochic acid exposure in Romania and implications for renal cell carcinoma.

ABSTRACT:

Background

Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.

Methods

We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N(6)-yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.

Results

We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10(8) DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.

Interpretation

Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.

SUBMITTER: Turesky RJ

PROVIDER: S-EPMC4716534 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Aristolochic acid exposure in Romania and implications for renal cell carcinoma.

Turesky Robert J RJ Yun Byeong Hwa BH Brennan Paul P Mates Dana D Jinga Viorel V Harnden Patricia P Banks Rosamonde E RE Blanche Helene H Bihoreau Marie-Therese MT Chopard Priscilia P Letourneau Louis L Lathrop G Mark GM Scelo Ghislaine G

British journal of cancer 20151210 1

<h4>Background</h4>Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.<h4>Methods</h4>We performed mass spectrometric measurements of the aristolactam (AL) DNA ad ...[more]

PMID: 26657656

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Project description:Renal cell carcinoma (RCC) is the most common type of cancer in kidney and is often diagnosed in advanced stages. Until now, there is no reliable biomarker to assess tumor prognosis during histopathological diagnosis. The Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) overexpression has been suggested as prognostic indicator for RCC, however, its protein profile needs to be clarified. This study investigated the MTHFD2 expression in different RCC cohorts, associating it with tumor characteristics and prognostic factors. Gene expression comparisons between non-neoplastic (NN) and tumor samples, as well as patients' survival analysis, were assessed using KM-Plotter tool. MTHFD2 protein pattern was evaluated in 117 RCC by immunohistochemistry and associations with prognosis, clinical and pathological data were investigated. The tumors exhibited higher MTHFD2 transcript levels than NN, being even higher in the metastatic group. Opposite gene expression patterns were found among clear cell renal cell carcinoma (ccRCC) and pappilary renal cell carcinoma (pRCC) subtypes, showing higher and lower expressions compared to NN samples respectively. Overexpression was associated with shorter overall survival for ccRCC and pRCC subtypes, and shorter recurrence-free survival for pRCC. The immunolabeling profile varied according to tumor subtypes, with lower intensity and expression scores in ccRCC compared to pRCC and to chromophobe renal cell carcinoma (chRCC). MTHFD2 protein expression was associated with larger tumors and higher Fuhrman grades. Although prognostic value of protein immunostaining was not confirmed, patients with higher MTHFD2 tended to have lower survival rates in the pRCC group. The results highlight MTHFD2 different patterns according to RCC histological subtypes, revealing marked variations at both the genetic and protein levels. The mRNA indicated tumor prognosis, and greater expression in the tumor samples. Although MTHFD2 immunolabeling suggests tumor aggressiveness, it needs to be validated in other cohorts as potential prognostic factor.

Dataset Information

Aristolochic acid exposure in Romania and implications for renal cell carcinoma.

Background

Methods

Results

Interpretation

Publications

Aristolochic acid exposure in Romania and implications for renal cell carcinoma.

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