Ritchie Miles (wealthsong3)
GenomePaint (https//genomepaint.stjude.cloud/) is an interactive visualization platform for whole-genome, whole-exome, transcriptome, and epigenomic data of tumor samples. Its design captures the inter-relatedness between DNA variations and RNA expression, supporting in-depth exploration of both individual cancer genomes and full cohorts. Regulatory non-coding variants can be inspected and analyzed along with coding variants, and their functional impact further explored by examining 3D genome data from cancer cell lines. Further, GenomePaint correlates mutation and expression patterns with patient outcomes, and supports custom data upload. We used GenomePaint to unveil aberrant splicing that disrupts the RING domain of CREBBP, discover cis activation of the MYC oncogene by duplication of the NOTCH1-MYC enhancer in B-lineage acute lymphoblastic leukemia, and explore the inter- and intra-tumor heterogeneity at EGFR in adult glioblastomas. These examples demonstrate that deep multi-omics exploration of individual cancer genomes enabled by GenomePaint can lead to biological insights for follow-up validation.Should lorlatinib be the standard first-line treatment in advanced ALK-rearranged lung cancer? In the New England Journal of Medicine, Shaw et al. present interim analysis results from CROWN, a randomized, phase 3 study comparing lorlatinib with crizotinib as initial therapy in patients with advanced ALK-rearranged NSCLC.The NCI-MATCH is a national master protocol trial, published in the Journal of Clinical Oncology, in which diverse tumors are sequenced and patients assigned to treatment. The trial demonstrates the feasibility of identifying rare and common actionable genetic alterations and underscores the strength of academic/community partnerships for improving trial access.Targeted protein degradation is an emerging technology for drug development. Zilurgisertib fumarate ic50 An article published in Nature reported a novel mechanism of targeted protein degradation triggered by small-molecule-induced polymerization of the oncogenic transcription factor BCL6.Abundant neoantigens are considered responsible for the immunotherapy sensitivity of mismatch repair-deficient (MMRd) cancers. In this issue of Cancer Cell, two papers show that MLH1 mismatch repair gene loss promotes cGAS-STING activation, interferon secretion, and T cell priming. This may be essential for the high immunotherapy sensitivity in MMRd cancer.In this issue of Cancer Cell, Wheeler et al. report that mechanisms of exceptional response to cancer treatment can be grouped into four broad categories dysregulated intracellular signaling pathways, altered DNA damage response, tumor microenvironment or immune engagement, and alterations associated with a favorable prognosis.Cancer research has been severely impacted by COVID-19. What does the future of cancer research look like in the new year after the pandemic?The transition from the Late Neolithic to the Bronze Age has witnessed important population and societal changes in western Europe.1 These include massive genomic contributions of pastoralist herders originating from the Pontic-Caspian steppes2,3 into local populations, resulting from complex interactions between collapsing hunter-gatherers and expanding farmers of Anatolian ancestry.4-8 This transition is documented through extensive ancient genomic data from present-day Britain,9,10 Ireland,11,12 Iberia,13 Mediterranean islands,14,15 and Germany.8 It remains, however, largely overlooked in France, where most focus has been on the Middle Neolithic (n = 63),8,9,16 with the exception of one Late Neolithic genome sequenced at 0.05× coverage.16 This leaves the key transitional period covering ∼3,400-2,700 cal. years (calibrated years) BCE genetically unsampled and thus the exact time frame of hunter-gatherer persistence and arrival of steppe migrations unknown. To remediate this, we sequenced 24 ancient human genomes from France spanning ∼3,400-1,600 cal. y
