A catalogue of cancer-driving mutations in healthy tissue

Bae‐Jump, Victoria L.; Levine, Douglas A.

doi:10.1038/d41586-020-01081-6

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…First, we demonstrated that, like epithelial cells, stromal cells surrounding glands in adenomyosis and peritoneal endometriosis can be of clonal origin because of somatic mutations detected. Likewise, as for eutopic endometrium, which has recently been reported to carry cancer-driving mutations in individual glands [29][30][31][32][33][34], we found somatic mutations in stroma alongside glandular epithelium. The lack of mutations detected in the stroma from some of the cases may have two explanations.…”

Section: LI Et Alsupporting

confidence: 79%

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Antero

Zhang

et al. 2021

The Journal of Pathology

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Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remains unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometriumrelated disorders.

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Section: LI Et Alsupporting

confidence: 79%

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Antero

Zhang

et al. 2021

The Journal of Pathology

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Putative homeostatic role of cancer driver mutations

Venkatachalam¹,

Pikarsky²,

Ben‐Neriah³

2022

Trends in Cell Biology

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Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management

Dörk

Hillemanns

Tempfer

et al. 2020

Cancers

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Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

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A catalogue of cancer-driving mutations in healthy tissue

Cited by 3 publications

References 13 publications

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Putative homeostatic role of cancer driver mutations

Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management

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