Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer

Haig, David

doi:10.1098/rstb.2014.0178

Cited by 38 publications

(33 citation statements)

References 127 publications

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“…Above all, this alteration in TP53 allele-specific expression ratios suggests that TP53 may be subject to genomic imprinting [35] in this LFS family. Although a role for genomic imprinting of TP53 in human oncogenesis has not yet been established, it has been implicated in mice [36], as well as for other tumor suppressors in humans [37].…”

Section: Discussionmentioning

confidence: 99%

Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li–Fraumeni syndrome

et al. 2017

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Li-Fraumeni Syndrome (LFS) is an autosomal dominant disorder where an oncogenic TP53 germline mutation is passed from parent to child. p53 is a key tumor suppressor regulating cell cycle arrest in response to DNA damage. Paradoxically, some mutant TP53 carriers remain unaffected, while their children develop cancer within the first few years of life. To address this paradox, response to UV stress was compared in dermal fibroblasts (dFb) from an affected LFS patient vs. their unaffected carrier parent. UV induction of CDKN1A/p21, a regulatory target of p53, in LFS patient dFb was significantly reduced compared to the unaffected parent. UV exposure also induced significantly greater p53[Ser15]-phosphorylation in LFS patient dFb, a reported property of some mutant p53 variants. Taken together, these results suggested that the unaffected parent dFb may express an increased proportion of wild-type vs. mutant p53. Indeed, a significantly increased ratio of wild-type to mutant TP53 allele-specific expression in the unaffected parent dFb was confirmed by RT-PCR-RFLP and RNA-seq analysis. Hence, allele-specific expression of wild-type TP53 may allow an unaffected parent to mount a response to genotoxic stress more characteristic of homozygous wild-type TP53 individuals than their affected offspring, providing protection from the oncogenesis associated with LFS.

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Section: Discussionmentioning

confidence: 99%

Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li–Fraumeni syndrome

et al. 2017

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“…Haig [43], working in the same vein as Boddy et al [42], argues that intra-genomic conflict has led to genes with carcinogenic functions, which may explain why animals, and particularly mammals, seem to be more cancer-prone than other forms of multicellularity [2,44]. Genes for placental development have evolved to invade maternal tissues and evade the maternal immune system.…”

Section: The Objectives Of This Issuementioning

confidence: 99%

Peto's paradox and the promise of comparative oncology

Nunney

Maley

Breen

et al. 2015

Phil. Trans. R. Soc. B

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'.Subject Areas: evolution, health and disease and epidemiology, molecular biology, physiology Keywords:Peto's paradox, comparative oncology, evolution, life-history theory, cancer, modelling The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of 'comparative oncology'. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with 'Peto's paradox', the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.

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“…Since transmissible cancer cell lines evolve on the evolutionary landscape of the host genomes, a sufficiently high prevalence of a transmissible cancer can result in a tug‐of‐war akin to host–parasite interactions between the selfish malignant cell lines and host genomes (sensu ‘Red‐Queen’ dynamics) . A recent study by Decker et al demonstrated such host adaptation to CTVT cells where potential resistance conferring mutations were observed in the dog genome in self‐antigen presentation (MHC), immune surveillance, genome integrity maintenance and cell apoptosis regulation pathways.…”

Section: Transmissible Cancer Invokes Adaptive Changes and Responses mentioning

confidence: 99%

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

et al. 2018

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Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease (DFTD), a transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii), provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts. Here we provide an overview of parasite-induced host life history (LH) adaptations, then both phenotypic plasticity of LH responses and changes in allele frequencies that affect LH traits of Tasmanian devils in response to DFTD are discussed. We conclude that akin to parasites, cancer can directly and indirectly affect devil LH traits and trigger host evolutionary responses. Consequently, it is important to consider oncogenic processes as a selective force in wildlife.

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Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer

Cited by 38 publications

References 127 publications

Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li–Fraumeni syndrome

Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li–Fraumeni syndrome

Peto's paradox and the promise of comparative oncology

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

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