A cloud‐based resource for genome coordinate‐based exploration and large‐scale analysis of chromosome aberrations and gene fusions in cancer

Abstract

Cytogenetic analysis provides important information on the genetic mechanisms of cancer. The Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (Mitelman DB) is the largest catalog of acquired chromosome aberrations, presently comprising >70 000 cases across multiple cancer types. Although this resource has enabled the identification of chromosome abnormalities leading to specific cancers and cancer mechanisms, a large-scale, systematic analysis of these aberrations and their downstream implications has been difficult due to the lack of a standard, automated mapping from aberrations to genomic coordinates. We previously introduced CytoConverter as a tool that automates such conversions. Cyto-Converter has now been updated with improved interpretation of karyotypes and has been integrated with the Mitelman DB, providing a comprehensive mapping of the 70 000+ cases to genomic coordinates, as well as visualization of the frequencies of chromosomal gains and losses. Importantly, all CytoConverter-generated genomic coordinates are publicly available in Google BigQuery, a cloud-based data warehouse, facilitating data exploration and integration with other datasets hosted by the Institute for Systems Biology Cancer Gateway in the Cloud (ISB-CGC) Resource. We demonstrate the use of BigQuery for integrative analysis of Mitelman DB with other cancer datasets, including a comparison of the frequency of imbalances identified in Mitelman DB cases with those found in The Cancer Genome Atlas (TCGA) copy number datasets. This solution provides opportunities to leverage the power of cloud computing for low-cost, scalable, and integrated analysis of chromosome aberrations and gene fusions in cancer.

Chromosomal Aberration t(14;17)(q32;q21) Simultaneously Activates HOXB5 and miR10a in Triple-Hit B-Cell Lymphoma

“…SC-1 is a B-cell lymphoma cell line derived from a 67-year-old male patient presenting with FL. Initial cytogenetic analysis revealed chromosomal rearrangement t(14;17)(q32;q21), representing an uncharacterized abnormality in hematopoietic malignancies [ 22 , 23 ]. In this study, we performed karyotyping ( Figure 1 A), FISH analysis ( Figure 1 B,C), and genomic profiling of SC-1 ( Supplementary Figure S2 ) to reveal cytogenetic abnormalities in this interesting cell line which displayed a hyperdiploid karyotype bearing multiple rearrangements previously associated with B-cell lymphoma together with novel changes selected for more detailed analysis.…”

Unearthed Novel Molecular Phenotypes and Potential Therapeutic Targets in Esophagogastric Adenocarcinoma

“…We identified gene fusions in NTRK1 and NTRK3, which are targetable by tropomyosin receptor kinase (TRK) inhibitors (41). Although fusions involving these genes have been found in multiple cancer types, including colorectal, lung, gastric, and rare cancers (42,43), we are first to describe the fusion partners in EGAC as verified using the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (44). Other targetable fusions involving MET (45) and NRG1 (46) were also identified.…”

NCI Cancer Research Data Commons: Cloud-Based Analytic Resources

“…In addition, ISB-CGC maintains another separately located database, caNanoLab ( https://cananolab.cancer.gov/ ). The Mitelman Database is the largest catalog of acquired chromosome aberrations available today, presently comprising >70,000 cases across multiple cancer types ( 6 ). The TP53 Database is a comprehensive database on variations in the tumor protein p53 gene ( TP53 ), one of the most frequently mutated genes in human cancer ( 7 ).…”