The mitotic apparatus protein NuMA has an intrinsic membrane-targeting mechanism that is regulated by CDK1-mediated phosphorylation, underlies anaphase-specific cortical accumulation of dynein, and contributes to chromosome separation.
equity in the company. KNK holds stock in Illumina, Inc. GRO is an employee of Foundation Medicine with equity in Roche. MVS is an employee of, and shareholder in, McKesson Corporation, and is a clinical advisor/serves on the advisory board for GRAIL. EAK is a consultant for GRAIL, Inc. and Cellanyx, LLC. The Mayo Clinic was compensated for MCL's advisory board activities for GRAIL, Inc.Research.
<div>AbstractPurpose:<p>We recently reported the development of a cell-free DNA (cfDNA) targeted methylation (TM)-based sequencing approach for a multi-cancer early detection (MCED) test that includes cancer signal origin prediction. Here, we evaluated the prognostic significance of cancer detection by the MCED test using longitudinal follow-up data.</p>Experimental Design:<p>As part of a Circulating Cell-free Genome Atlas (CCGA) substudy, plasma cfDNA samples were sequenced using a TM approach, and machine learning classifiers predicted cancer status and cancer signal origin. Overall survival (OS) of cancer participants in the first 3 years of follow-up was evaluated in relation to cancer detection by the MCED test and clinical characteristics.</p>Results:<p>Cancers not detected by the MCED test had significantly better OS (<i>P</i> < 0.0001) than cancers detected, even after accounting for other covariates, including clinical stage and method of clinical diagnosis (i.e., standard-of-care screening or clinical presentation with signs/symptoms). Additionally, cancers not detected by the MCED test had better OS than was expected when data were adjusted for age, stage, and cancer type from the Surveillance, Epidemiology, and End Results (SEER) program. In cancers with current screening options, the MCED test also differentiated more aggressive cancers from less aggressive cancers (<i>P</i> < 0.0001).</p>Conclusions:<p>Cancer detection by the MCED test was prognostic beyond clinical stage and method of diagnosis. Cancers not detected by the MCED test had better prognosis than cancers detected and SEER-based expected survival. Cancer detection and prognosis may be linked by the underlying biological factor of tumor fraction in cfDNA.</p></div>
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