Unknown,Transcriptomics,Genomics,Proteomics

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WG-DASL expression profiling of formalin-fixed paraffin embedded primary breast tumours and matched lymph node metastases across four clinically relevant metastatic groups

ABSTRACT: The development of metastases is a complex multi-step process manifested by diverse patterns, involving single or multiple organs and different time-courses of distant recurrences. The aim of this study was to characterise molecular patterns associated with patterns of organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases. This study includes patients with four patterns of first metastatic sites: bone only (with no visceral metastases within 6 months of first metastasis); to viscera only (with no bone metastasis within 6 months of first metastasis); to bone and visceral organs within a 6 month period; and no recorded distant metastasis. The study population was composed of 5,061 patients diagnosed with invasive primary breast cancer without distant metastasis at the time of diagnosis between 1975 and 2005 from Guyâs Hospital. From the study population, an incidence-based case-control design was used to include patients from each of the metastatic groups and a control series randomly matched to cases according to having no reported metastasis up to the calendar date of metastasis. The aim of this expression profiling study was to characterise any molecular patterns that may be associated with the organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases.

ORGANISM(S): Homo sapiens

SUBMITTER: Kayleigh Ougham

PROVIDER: E-MTAB-4003 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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).

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WG-DASL expression profiling of formalin-fixed paraffin embedded primary breast tumours and matched lymph node metastases across four clinically relevant metastatic groups

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