Dataset Information

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.

ABSTRACT:

Background

The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.

Methods

Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.

Results

Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 x 10(-5)). SEMA3A knockdown enhanced radiation resistance.

Conclusions

This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.

SUBMITTER: Michikawa Y

PROVIDER: S-EPMC2928773 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Publications

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.

Michikawa Yuichi Y Suga Tomo T Ishikawa Atsuko A Hayashi Hideki H Oka Akira A Inoko Hidetoshi H Iwakawa Mayumi M Imai Takashi T

BMC medical genetics 20100811

<h4>Background</h4>The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.<h4>Methods</h4>Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less ( ...[more]

PMID: 20701746

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Project description:BackgroundPromoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets.Methods and findingsIn an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors.ConclusionsBy using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.

Dataset Information

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.

Background

Methods

Results

Conclusions

Publications

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.

Similar Datasets

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