Genetic and Epigenetic Intratumor Heterogeneity Impacts Prognosis of Lung Adenocarcinoma
Angela C. Pesatori,
Neil E. Caporaso,
Maria Teresa Landi
Posted 14 Dec 2019
medRxiv DOI: 10.1101/2019.12.09.19013672
Posted 14 Dec 2019
Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). We investigated ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 LUAD patients. We found substantial SCNA and methylation ITH, and clonal architecture analyses showed congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Interestingly, methylation ITH mapping to gene promoter areas or tumor suppressor genes was low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes was found in several tumors. To quantify ITH for valid statistical association analyses we developed an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. APITH indexes for SCNAs and methylation aberrations were both significantly associated with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD.
- Downloaded 269 times
- Download rankings, all-time:
- Site-wide: 114,348
- In genetic and genomic medicine: 617
- Year to date:
- Site-wide: 106,386
- Since beginning of last month:
- Site-wide: 125,545
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!