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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer

ABSTRACT: Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer

PROVIDER: PRJNA798619 | ENA |

REPOSITORIES: ENA

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	SRR17660983.fastq.gz	Fastqsanger.gz

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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [cell lines]

Project description:Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [cell lines]

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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [Human tumor]

Project description:Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [Human tumor]

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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [Human tumor]

Project description:Intratumoral heterogeneity underlies cancer treatment resistance, but approaches to neutralize it remain elusive. Here, we recast heterogeneity in a systems perspective that considers cancer cell functional tasks inherited from cells of origin. We apply Archetype Analysis to bulk transcriptomics data from small cell lung cancer (SCLC), which forms tumors composed of neuroendocrine (NE) and non-neuroendocrine (non-NE) transcriptional subtypes. SCLC subtypes fit well in a 5-dimensional polytope whose vertices optimize tasks reminiscent of pulmonary NE cells, the SCLC normal counterpart, and include injury repair, slithering, and chemosensation. SCLC cells near a vertex are specialists for a task, while more distant cells are generalists, bearing gene signatures of multiple archetypes. Evolutionary theory and dynamical systems modeling suggest a division of labor strategy for adaptation to treatment, based on task trade-offs amongst specialists and generalists. Cell Transport Potential, a metric derived from single-cell RNA velocity, uncovers plasticity trends from specialists to generalists, and NE to non-NE subtypes. Transcription factor network simulations indicate that MYC overexpression increases plasticity by de-stabilizing NE subtypes. Framing heterogeneity in archetype space provides insights into transformative cancer treatments aimed at tumor cell plasticity.

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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer [cell lines]

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Intratumoral heterogeneity in cholangiocarcinoma

Project description:Intratumoral heterogeneity in cholangiocarcinoma

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Archetype tasks link intratumoral heterogeneity to plasticity in recalcitrant small cell lung cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-05 | GSE193961 | GEO

Intratumoral heterogeneity of prostate cancers

Project description:Copy number analyses of regionally separated intratumoral biopsies of prostate cancers. Intratumoral heterogeneity (ITH) leads to regional biases of the mutational landscape in a single tumor and may influence the single biopsy-based clinical diagnosis and treatment decision. To evaluate the extent of ITH in unifocal prostate cancers (PCAs) that had not been sought, we analyzed multiple regional biopsies from three PCAs using DNA copy number analyses. DNA copy number showed ITH including regional biases in the presentation of a well-known driver of TMPRSS2-ERG fusion. Our analyses identified a substantial level of genetic ITH in unifocal PCAs at the genomic levels, which should be taken into account for the curation of biomarkers in the clinical setting. Four intratumoral biopsies were obtained per tumor for three prostate cancers. Radical prostatectomy tissue from three patients with prostate cancers were obtained. Board-certified pathologists reviewed the hematoxylin&eosin stained sections and identified tumor-rich regions (> 80% purity). We selected four different areas for biopsy that were at least 5mm apart and were comprised of the most common Gleason pattern (the most common histologic patterns with minimal histologic differences). Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.

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Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). 138 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. RNA extracted fresh frozen tissue samples.

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Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC).

2015-05-25 | GSE65615 | GEO

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