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Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

ABSTRACT: Background:Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging. Patients and methods:Here, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo 'stopwatch'. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively 'carbon date' the malignant progression. Results:The primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity. Conclusion:Our data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate.

SUBMITTER: Lote H

PROVIDER: S-EPMC5452067 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

Lote H H Spiteri I I Ermini L L Vatsiou A A Roy A A McDonald A A Maka N N Balsitis M M Bose N N Simbolo M M Mafficini A A Lampis A A Hahne J C JC Trevisani F F Eltahir Z Z Mentrasti G G Findlay C C Kalkman E A J EAJ Punta M M Werner B B Lise S S Aktipis A A Maley C C Greaves M M Braconi C C White J J Fassan M M Scarpa A A Sottoriva A A Valeri N N

Annals of oncology : official journal of the European Society for Medical Oncology 20170601 6

<h4>Background</h4>Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging.<h4>Patients and methods</h4>Here, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urina ...[more]

PMID: 28327965

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Project description:In archaeological research, changes in material culture and the evolution of styles are taken as major indicators for socio-cultural transformation. They form the basis for typo-chronological classification and the establishment of phases and periods. Central European Bronze Age material culture from burials reveals changes during the Bronze Age and represents a perfect case study for analyzing phenomena of cultural change and the adoption of innovation in the societies of prehistoric Europe. Our study focuses on the large-scale change in material culture which took place in the second millennium BC and the emergence at the same period of new burial rites: the shift from inhumation burials in flat graves to complex mounds and simple cremation burials. Paul Reinecke was the first to divide the European Bronze Age (EBA) into two phases, Bz A1 and A2. The shift from the first to the second phase has so far been ascribed to technical advances. Our study adopted an innovative approach to quantifying this phenomenon. Through regressive reciprocal averaging and Bayesian analysis of radiocarbon-dated grave contexts located in Switzerland and southern Germany, we modelled chronological changes in the material culture and changes in burial rites in these regions in a probabilistic way. We used kernel density models to summarize radiocarbon dates, with the aim of visualizing cultural changes in the third and second millennium BC. In 2015, Stockhammer et al. cast doubt on the chronological sequence of the Reinecke phases of the EBA on the basis of newly collected radiocarbon dates from southern Germany. Our intervention is a direct response to the results of that study. We fully agree with Stockhammer's et al. dating of the start of EBA, but propose a markedly different dating of the EBA/MBA transition. Our modelling of radiocarbon data demonstrates a statistically significant typological sequence of phases Bz A1, Bz A2 and Bz B and disproves their postulated chronological overlap. The linking of the archaeological relative-chronological system with absolute dates is of major importance to understanding the temporal dimension of the EBA phases.

Dataset Information

Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

Publications

Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

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