Benefit of a second opinion, intrapulmonary metastases or multiple primary tumors?
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Oscar Krijgsman
PROVIDER: E-GEOD-42377 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2012-11-20 | GSE42377 | GEO
Project description:In this study our aim was to document recurrent DNA copy number aberration associated breakpoints in primary tumors of colorectal cancer patients that ultimately received systemic treatment in the context of metastatic disease. Such data can be used to catalogue copy number aberration associated breakpoints and thereby affected genes. To this end, high quality arrayCGH data set of clinically well annotated colorectal cancer specimens was generated using FFPE tumor samples from patients from two phase III clinical trials, namely CAIRO and CAIRO2. arrayCGH data of colorectal cancers of patients from 2 clinical trials. 108 patients were treated with capecitabine first line, 110 patients were treated with capecitabine and irinotecan first line and 134 patients were treated with capecitabine, oxaliplatin and bevacizumab.
2014-11-14 | E-GEOD-63216 | biostudies-arrayexpress
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).
2014-02-10 | E-GEOD-38479 | biostudies-arrayexpress
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy. aCGH data of colorectal cancers of patients from 2 clinical trials (CAIRO, CAIRO2). 105 patients were treated with capecitabine first line (CAIRO arm A), 111 patients were treated with capecitabine and irinotecan first line (CAIRO arm B), and 133 patients were treated with capecitabine, oxaliplatin and bevacizumab (CAIRO2 arm A).
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