Integrated metabolic and genetic analysis reveals distinct features of human differentiated thyroid cancer

Cararo-Lopes, Eduardo; Sawant, Akshada; Moore, Dirk F.; Ke, Hua Zhu; Shi, Fuqian; Laddha, Saurabh V.; Chen, Ying; Sharma, Anchal; Naumann, Jake; Guo, Jessie Yanxiang; Gómez, Marı́a; Ibrahim, Maria Salem; Smith, Tracey L.; Riedlinger, Gregory; Lattime, Edmund C.; Trooskin, Stanley Z.; Ganesan, Shridar; Su, Xiaoyang; Pasqualini, Renata; Arap, Wadih; De, Subhajyoti; Chan, Chang S.; White, Eileen

doi:10.1002/ctm2.1298

Cited by 9 publications

(1 citation statement)

References 82 publications

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“…The final BAM files were also marked as duplicated, sorted, and indexed using GATK tools. GATK Mutect2 was used for somatic mutation calling with a panel of normal and tumor normal paired mode as described previously [63, 64], and mutect-filter in GATK Mutect2 was used for an initial filter on the variants. A hard filter was also performed using bcftools v1.11-3 (GigaScience), with tumor AD (Allelic depths for the ref and alt alleles in the order listed) >=3, DP (Approximate read depth (reads with MQ=255 or with bad mates are filtered)) >=10 for tumor and normal both, and tumor AF (Allele fractions of alternate alleles in the tumor) >=0.1.…”

Section: Methodsmentioning

confidence: 99%

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes

Sawant,

Shi,

Lopes

et al. 2024

Preprint

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Mutations in polymerasesPold1andPoleexonuclease domains in humans are associated with increased cancer incidence, elevated tumor mutation burden (TMB) and response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond. Here we generatedPold1andPoleproofreading mutator mice and show that ICB treatment of mice with high TMB tumors did not improve survival as only a subset of tumors responded. Similarly, introducing the mutator alleles into mice with Kras/p53 lung cancer did not improve survival, however, passaging mutator tumor cellsin vitrowithout immune editing caused rejection in immune-competent hosts, demonstrating the efficiency by which cells with antigenic mutations are eliminated. Finally, ICB treatment of mutator mice earlier, before observable tumors delayed cancer onset, improved survival, and selected for tumors without aneuploidy, suggesting the use of ICB in individuals at high risk for cancer prevention.HighlightsGermline somatic and conditionalPold1andPoleexonuclease domain mutations in mice produce a mutator phenotype.Spontaneous cancers arise in mutator mice that have genomic features comparable to human tumors with these mutations.ICB treatment of mutator mice with tumors did not improve survival as only a subset of tumors respond.Introduction of the mutator alleles into an autochthonous mouse lung cancer model also did not produce immunogenic tumors, whereas passaging mutator tumor cellsin vitrocaused immune rejection indicating efficient selection against antigenic mutationsin vivo.Prophylactic ICB treatment delayed cancer onset, improved survival, and selected for tumors with no aneuploidy.Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes

Sawant,

Shi,

Lopes

et al. 2024

Preprint

Self Cite

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Minimally invasive biopsy‐based diagnostics in support of precision cancer medicine

Franzén,

Auer,

Lewensohn

2024

Molecular Oncology

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Precision cancer medicine (PCM) to support the treatment of solid tumors requires minimally invasive diagnostics. Here, we describe the development of fine‐needle aspiration biopsy‐based (FNA) molecular cytology which will be increasingly important in diagnostics and adaptive treatment. We provide support for FNA‐based molecular cytology having a significant potential to replace core needle biopsy (CNB) as a patient‐friendly potent technique for tumor sampling for various tumor types. This is not only because CNB is a more traumatic procedure and may be associated with more complications compared to FNA‐based sampling, but also due to the recently developed molecular methods used with FNA. Recent studies show that image‐guided FNA in combination with ultrasensitive molecular methods also offers opportunities for characterization of the tumor microenvironment which can aid therapeutic decisions. Here we provide arguments for an increased implementation of molecular FNA‐based sampling as a patient‐friendly diagnostic method, which may, due to its repeatability, facilitate regular sampling that is needed during different treatment lines, to provide tumor information, supporting treatment decisions, shortening lead times in healthcare, and benefit healthcare economics.

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Clinical and translational mode of single‐cell measurements: An artificial intelligent single cell

Wang,

Powell,

et al. 2024

Clinical and Translational Dis

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With rapid development and mature of single‐cell measurements, single‐cell biology and pathology become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single‐cell measurements for clinical practice, translate the signals of single‐cell systems biology into determination of clinical phenotype, and predict patient response to therapies. The present Perspective proposes a new system coined as the clinical artificial intelligent single‐cell (caiSC) with the dynamic generator of clinical single‐cell informatics, artificial intelligent analysers, molecular multimodal reference boxes, clinical inputs and outs, and AI‐based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single‐cell level. The caiSC represents an important step and milestone to translate the single‐cell measurement into clinical application, assit clinicians’ decision‐making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.

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Integrated metabolic and genetic analysis reveals distinct features of human differentiated thyroid cancer

Cited by 9 publications

References 82 publications

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes

Minimally invasive biopsy‐based diagnostics in support of precision cancer medicine

Clinical and translational mode of single‐cell measurements: An artificial intelligent single cell

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