Clonality and timing of relapsing colorectal cancer metastasis revealed through whole-genome single-cell sequencing

Alves, João M.; Prado‐Lopez, Sonia; Tomás, Laura; Valecha, Mónica; Estévez-Gómez, Nuria; Alvariño, Pilar; Geissel, Dominik; Modest, Dominik Paul; Sauer, Igor M.; Pratschke, Johann; Raschzok, Nathanael; Sers, Christine; Mamlouk, Soulafa; Posada, David

doi:10.1016/j.canlet.2022.215767

Cited by 10 publications

(4 citation statements)

References 67 publications

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“…Previous studies have reported that gut microbiome dysbiosis could promote in ammation, tissue impairment and disruption of gastrointestinal (GI) barrier, all of which can lead to carcinogenesis [1,2,5,9,10]. Similarly, the dysbiosis of oral microbiota has also been proven to be associated not only to oral diseases but also to systemic ones such as colorectal cancer (CRC), the second most deadly type of cancer, in many cases due to liver metastasis with relapses of the disease after several months [11,12].…”

Section: Introductionmentioning

confidence: 99%

Evidence for translocation of oral Parvimonas micra from the subgingival sulcus of the human oral cavity to the colorectal adenocarcinoma

Conde‐Pérez

Buetas

Aja‐Macaya

et al. 2022

Preprint

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Background: The carcinogenesis of colorectal cancer (CRC) is a multifactorial process involving both environmental and host factors, such as human genetics or the gut microbiome, which in CRC patients appears to be enriched in oral microorganisms. The aim of this work was to investigate the presence and activity of Parvimonas micrain CRC patients. To do that, samples collected from subgingival sulcus and neoplastic lesions were used for culturomics. Then, samples from different body locations (saliva, gingival crevicular fluid, feces, non-neoplastic colon mucosa, transition colon mucosa, adenocarcinoma, adenomas, metastatic and non-neoplastic liver samples) were used for 16S rRNA metabarcoding and metatranscriptomics. Whole genome sequencing was conducted for all P. micrastrains obtained. Results: Several P. micraisolates from the oral cavity and adenocarcinoma tissue from CRC patients were obtained. The comparison of oral and tumoral P. micra genomes identified that a pair of clones (PM89KC) were 99.2% identical between locations in one CRC patient, suggesting that the same clone migrated from oral cavity to the gut. The 16S rRNA metabarcoding analysis of samples from this patient revealed that P. micra cohabits with other periodontal pathogens such as Fusobacterium, Prevotella or Dialister, both in the intestine, liver and the subgingival space, which suggests that bacterial translocation from the subgingival environment to the colon or liver could be more efficient if these microorganisms travel together forming a synergistic consortium. In this way, bacteria might be able to perform tasks that are impossible for single cells. In fact, RNA-seq of the adenocarcinoma tissue confirmed the activity of these bacteria in the neoplastic tissue samples and revealed that different oral species, including P. micra, were significantly more active in the tumor compared to non-neoplastic tissue from the same individuals. Conclusion: P. micra appears to be able to translocate from the subgingival sulcus to the gut, where oral bacteria adapt to the new niche and could have a relevant role in carcinogenesis. According to our findings, periodontal disease, which increases the levels of these pathogens and facilitates their dissemination, could represent a risk factor for CRC development and P. micra could be used as a non-invasive CRC biomarker.

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Section: Introductionmentioning

confidence: 99%

Evidence for translocation of oral Parvimonas micra from the subgingival sulcus of the human oral cavity to the colorectal adenocarcinoma

Conde‐Pérez

Buetas

Aja‐Macaya

et al. 2022

Preprint

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“… 48 SRA: SRP067815 scDNA WES data Wu Wu et al. 85 SRA: SRP067815 scDNA WES data Xu Xu et al. 86 SRA: SRA050201 scDNA WES data Ni Ni et al.…”

Section: Methodsmentioning

confidence: 99%

Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues

Borgsmüller,

Valecha,

Kuipers

et al. 2023

Cell Genomics

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“…An original dataset containing whole genomes analysis from 60 single-cell collecting samples before therapy and after metastatic relapse resection demonstrated that three non-synonymous and one stop codon mutations specific to the recurrent lineage in four different genes, PKHD1, PCDHB15, CSF1R, and CC2D1B, were detected in CRC patients. Moreover, a distinctive mutagenic prototype distinguishing the cancer cells from the recurrent lesion illustrated by a substantial contribution of COSMIC signatures SBS35 and SBS17b was identified ( 112 ).…”

Section: Comprehensive Genetic Analysismentioning

confidence: 99%

Current status and perspectives of genetic testing in gastrointestinal cancer (Review)

Matsuoka,

Yashiro

2023

Oncol Lett

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Genetic testing has become widespread in daily medical care for gastrointestinal (GI) cancers. However, unlike breast cancer and non-small cell lung cancer, in which personalized medicine targeting various driver genes is standardized, the incidence of targeted gene abnormalities in GI cancers is low. Nevertheless, such abnormalities may be linked to therapeutic agents and the further development of therapeutic agents for personalized medicine for GI cancers is desired. A liquid biopsy is of great benefit in offering clinical decision support, in applications such as GI cancer screening, surgical interventions, monitoring disease status and enhancing patient survival outcomes, all of which would contribute to personalized medicine. Germline genetic testing is required for several types of GI cancer, which shows clinical indications of hereditary predisposition. The increasing use of multigene panel testing has redefined gene-cancer associations, and consequently the estimate of cancer risk that vary from low to high penetrance. Comprehensive genetic testing can enable the detection of novel treatment targets and the discovery of undefined multiple diagnostic/predictive markers, which may enhance the molecular-level understanding of GI cancers. Genetic testing can also aid the design of more appropriate and adequate genomic-driven therapies for patients who may benefit from other standardized therapeutic methods.

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Clonality and timing of relapsing colorectal cancer metastasis revealed through whole-genome single-cell sequencing

Cited by 10 publications

References 67 publications

Evidence for translocation of oral Parvimonas micra from the subgingival sulcus of the human oral cavity to the colorectal adenocarcinoma

Evidence for translocation of oral Parvimonas micra from the subgingival sulcus of the human oral cavity to the colorectal adenocarcinoma

Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues

Current status and perspectives of genetic testing in gastrointestinal cancer (Review)

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