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Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes.
(WILEY, 2020-01-22)
BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking. ...
Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
(ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-30)
The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in ...
Subclonal reconstruction of tumors by using machine learning and population genetics.
(NATURE PUBLISHING GROUP, 2020-09-01)
Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ...
Evolutionary dynamics of neoantigens in growing tumors.
(NATURE PORTFOLIO, 2020-10-01)
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ...
Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.
(NATURE PORTFOLIO, 2020-03-27)
Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving ...
Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates CDX2 gain as a predictor of recurrence.
(WILEY, 2019-04-01)
Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention; however, recurrence ...
Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.
(BMC, 2018-05-31)
BACKGROUND: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic ...
Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells.
(NATURE RESEARCH, 2020-10-28)
Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply ...
Geospatial immune variability illuminates differential evolution of lung adenocarcinoma.
(NATURE PORTFOLIO, 2020-07-01)
Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1-5. However, the spatial configurations of immune and stromal cells, which may shed light on ...
Very large hidden genetic diversity in one single tumor: evidence for tumors-in-tumor.
(OXFORD UNIV PRESS, 2022-12-12)
Despite the concern of within-tumor genetic diversity, this diversity is in fact limited by the kinship among cells in the tumor. Indeed, genomic studies have amply supported the 'Nowell dogma' whereby cells of the same ...