The evolution of tumour phylogenetics: principles and practice

Schwartz, Russell; Schäffer, Alejandro A.

doi:10.1038/nrg.2016.170

Cited by 276 publications

(244 citation statements)

References 191 publications

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“…It is still unclear how these small genetic lesions interact with clinical tumor progression or contribute to possible resistance to treatment . Regardless, many of these subclones, while being genetically distinct, do share identical driver mutations …”

Section: Discussionmentioning

confidence: 99%

Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

Sanfrancesco

Eble

Grignon

et al. 2017

Molecular Carcinogenesis

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Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.

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Section: Discussionmentioning

confidence: 99%

Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

Sanfrancesco

Eble

Grignon

et al. 2017

Molecular Carcinogenesis

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“…36 Our aim was to use the distribution and AF of treatment-induced mutations to augment a phylogenetic tree with timing information. 36 Our aim was to use the distribution and AF of treatment-induced mutations to augment a phylogenetic tree with timing information.…”

Section: A Phylogenetic Model For Tumour Growth and Spreadmentioning

confidence: 99%

The genomic imprint of cancer therapies helps timing the formation of metastases

Németh

Krzystanek

Reiniger

et al. 2019

Intl Journal of Cancer

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A retrospective determination of the time of metastasis formation is essential for a better understanding of the evolution of oligometastatic cancer. This study was based on the hypothesis that genomic alterations induced by cancer therapies could be used to determine the temporal order of the treatment and the formation of metastases. We analysed the whole genome sequence of a primary tumour sample and three metastatic sites derived from autopsy samples from a young never‐smoker lung adenocarcinoma patient with an activating EGFR mutation. Mutation detection methods were refined to accurately detect and distinguish clonal and subclonal mutations. In comparison to a panel of samples from untreated smoker or never‐smoker patients, we showed that the mutagenic effect of cisplatin treatment could be specifically detected from the base substitution mutations. Metastases that arose before or after chemotherapeutic treatment could be distinguished based on the allele frequency of cisplatin‐induced dinucleotide mutations. In addition, genomic rearrangements and late amplification of the EGFR gene likely induced by afatinib treatment following the acquisition of a T790M gefitinib resistance mutation provided further evidence to tie the time of metastasis formation to treatment history. The established analysis pipeline for the detection of treatment‐derived mutations allows the drawing of tumour evolutionary paths based on genomic data, showing that metastases may be seeded well before they become detectable by clinical imaging.

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“…5C), in which DNA damage response (DDR), mismatch repair, aneuploidy and similar processes play a role, increasing the mutation load of developing tumors (69). Given that trajectories of mutations appear to follow detectable patterns (70,71,72) and that nutrient-sensing and metabolic pathways have been reported to interfere with DDR (73), also this biological process may open new ways to drug discovery.…”

Section: Figurementioning

confidence: 99%

Beyond Computational Genomics towards Systems Metabolomics for Precision Oncology

Alberghina¹

2018

Preprint

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Coordinated sets of extremely numerous digital data, on a given social or economic event, are treated by Artificial Intelligence tools to obtain reasonably accurate, valuable predictions. The same approach, applied to biomedical issues, as how to choose the right drug to completely cure a given cancer patient, does not reach satisfactory results. It is the "organized biological complexity", which requires a different systems approach, to integrate, in an Augmented Intelligence strategy, statistical computations of digital data, network construction of "omics" findings, well-designed mathematical models and new experiments in an iterative pathway to reconstruct the "logic" beneath the "organized complexity", as shown here for Systems Metabolomics of cancer. On this basis new diagnostic approaches, able to identify precision drug treatments, as well as new discovery strategy for more effective anti-cancer drugs are described.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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The evolution of tumour phylogenetics: principles and practice

Cited by 276 publications

References 191 publications

Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra‐ and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

The genomic imprint of cancer therapies helps timing the formation of metastases

Beyond Computational Genomics towards Systems Metabolomics for Precision Oncology

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