Publications by authors named "P Van Loo"
Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline and carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors.
View Article and Find Full Text PDFDisruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue.
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- Oral potentially malignant disorders (OPMDs) with genomic changes have a higher chance of turning into oral squamous cell carcinoma (OSCC), and while tissue biopsies provide genomic data, they are invasive.
- This pilot study explores the effectiveness of non-invasive brush biopsies in profiling the genomic landscape of a patient with both OPMD and OSCC, revealing that brush biopsies accurately captured 90% of single nucleotide variants (SNVs) and matched copy number profiles with tissue biopsies.
- The results suggest that brush biopsies can identify shared genomic alterations between OPMD and OSCC lesions, showcasing their potential for understanding tumor evolution and ancestry without the need for invasive procedures.
Article Synopsis
- Oncogenes can become activated through mechanisms like enhancer hijacking and mutations that generate new enhancers or promoters, helping researchers understand variations in noncoding cancer genomes.
- A new mechanism is identified where the loss of an intronic element in the FTO gene causes abnormal expression of the IRX3 oncogene in T cell acute lymphoblastic leukemia (T-ALL).
- The study suggests that 'promoter tethering' helps keep oncogenes inactive by linking them to non-functioning parts of the genome, which may act as a safeguard against tumor development.
We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion.
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