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A. Tangoku
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-049 - The MRE11/RAD50/NBS1 Complex Was Impaired in Lung Cancer from Chromate-Exposed Workers (ID 2536)
09:30 - 09:30 | Author(s): A. Tangoku
- Abstract
Background:
Our previous studies demonstrated that one third of lung cancers of chromate-exposed workers (chromate LC) showed high-degree microsatellite instability (MSI), most of which repressed DNA mismatch repair (MMR) hMLH1protein. MMR-deficient tumors are characterized by widespread changes in the number of microsatellites accumulating in both coding and non-coding sequences of many human genes. The MRE11–RAD50–NBS1 complex is essential for DNA double-strand break (DSB) repair performing by homologous recombination (HR) or non-homologous end joining (NHEJ). In gastric and colorectal cancers with MSI, the mono- or biallelic deletions in the poly(T)11 within MRE11 intron 4 and the frameshift mutations in the (A)9 repeat in RAD50 exon 13 were detected and the significant reduction of both proteins were identified.
Methods:
We used formalin-fixed paraffin-embedded materials from 36 chromate LC (28 cases; all male, mean age 56.8, squamous cell ca (SQ) 35, stage I 27, BI=488, mean chromate exposure 24 years) and 28 non-chromate LC (all male, mean age 61, SQ 28, stage I 8, BI=674). DNA was extracted and amplified using nested-PCR. The fragment analysis was performed using a capillary electrophoresis and GeneScan Analysis software (Applied Biosystem, USA).
Results:
In the poly(T)11 within MRE11 intron 4, 8 (29%) of 28 non-chromate LC showed 1bp deletion or insertion and 14 (52%) of 33 chromate LC showed 1bp deletion or insertion. In the (A)9 repeat in RAD50 exon 13, none of 27 non-chromate LC showed deletion or insertion and 4 (16%) of 25 chromate LC showed deletion. 67% of chromate LC with more than 3 MSI had abnormality of MRE11 gene, and 60% of chromate LC with 2 MSI had it. While, 27% of chromate LC with less than one MSI and 28% of non-chromate LC had it. 17% of chromate LC with more than 3 MSI had abnormality of MRE11 gene, and 10% of chromate LC with 2 MSI had it. While, 25% of chromate LC with less than one MSI had it and none of non-chromate LC had it.
Conclusion:
Half of chromate LC had the abnormality of the poly(T)11 within MRE11, which was associated with the degree of MSI. Sixteen percentage of chromate LC had the abnormality of the (A)9 repeat in RAD50. The carcinogenesis of chromate LC may be involved in the abnormality of DNA repair MRE11–RAD50–NBS1 complex.
