Deciphering the Evolutionary History of Complex Rearrangements in Head and Neck Cancer Patients Using Multi-Omic Approach
Chae, J.; Lee, J. S.; Park, J.; Lee, D.-S.; Park, W. S.; Clock, B.; Dixon, J.; Jung, Y.-S.; Hong, D.
Show abstract
Despite the large efforts in international cancer genome consortium studies, there are still a large proportion of tumors with complex genomic rearrangement often remained without a clinically relevant molecular characterization. Integration of multi-omic data helps elucidating evolutionary history of such cases and identifying predictive molecular markers. Here we present the findings of our proof-of-principle study that investigated the evolutionary history of complex rearrangements in primary head and neck tumor genomes integrating long-read whole-genome, Hi-C, and RNA sequencing. We report a HPV-positive case with development of complex genomic rearrangements tracing back to HPV-mediated genomic instability and a HPV-negative case with an enhancer hi-jacking in a region of chromothripsis predicted to co-occur with a neoloop and a super-enhancer. These structural alterations resulted in overexpression of the oncogenes CCND1 and ALK, respectively, validated with immunohistochemistry assay. Furthermore, we introduce a novel analytic approach utilizing long-read whole-genome data distinguishing somatic mutations before and after structural variants. Our findings highlight the need for multi-modal sequencing strategies to increase our understanding of cancer evolution and rare biomarkers in poorly understood cancers.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cancer Driver Topologically Associated Domains identify oncogenic and tumor suppressive lncRNAs 93%
- Long-read RNA sequencing redefines the clear cell renal cell carcinoma transcriptome and reveals novel genes and transcripts associated with disease recurrence and immune evasion 92%
- Accurately estimating pathway activity in single cells for clustering and differential analysis 92%
Similar papers in this journal
- Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells 93%
- Systematic lncRNA mapping to genome-wide co-essential pathways uncovers cancer dependency on uncharacterized lncRNAs 93%
- Single-cell profiling reveals the intratumor heterogeneity and immunosuppressive microenvironment in cervical adenocarcinoma 93%
Similar papers in this journal
- ERVcancer: a web resource designed for querying activation of human endogenous retroviruses across major cancer types 94%
- Improved in situ sequencing for high-resolution targeted spatial transcriptomic analysis in tissue sections 92%
- Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants 92%
Similar papers in this journal
- The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells 94%
- Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients 92%
- Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer 92%
Similar papers in this journal
- Genome profiles of lymphovascular breast cancer cells reveal multiple clonally differentiated outcomes with multi-regional LCM and G&T-seq 93%
- Evaluation of homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional tissue-based immunofluorescence assays 92%
- Predicting Endometrial Cancer Subtypes and Molecular Features from Histopathology Images Using Multi-resolution Deep Learning Models 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.