Dataset Information

Study of renal cancers and renal cancer metastases

ABSTRACT: Study of primary renal cancers as well as metastases derived from renal cancers in various distant organs.

PROVIDER: EGAS00001001176 | EGA |

REPOSITORIES: EGA

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Publications

Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes.

Winter Stefan S Fisel Pascale P Büttner Florian F Rausch Steffen S D'Amico Debora D Hennenlotter Jörg J Kruck Stephan S Nies Anne T AT Stenzl Arnulf A Junker Kerstin K Scharpf Marcus M Hofmann Ute U van der Kuip Heiko H Fend Falko F Ott German G Agaimy Abbas A Hartmann Arndt A Bedke Jens J Schwab Matthias M Schaeffeler Elke E

Scientific reports 20160720

Current therapies for metastatic clear cell renal cell carcinoma (ccRCC) show limited efficacy. Drug efficacy, typically investigated in preclinical cell line models during drug development, is influenced by pharmacogenes involved in targeting and disposition of drugs. Here we show through genome-wide DNA methylation profiling, that methylation patterns are concordant between primary ccRCC and macro-metastases irrespective of metastatic sites (rs ≥ 0.92). However, 195,038 (41%) of all investigat ...[more]

PMID: 27435027

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Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor. In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH).

Dataset Information

Study of renal cancers and renal cancer metastases

Publications

Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes.

Similar Datasets

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