Are solid tumours different in children with Down's syndrome?

Satgé, Daniel; Sasco, Annie J.; Lacour, Brigitte

doi:10.1002/ijc.11212

Cited by 22 publications

(29 citation statements)

References 10 publications

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“…Also, the percentage of cells in S phase in solid tumors, which are mostly aneuploid, varies between 2 − 8%, whereas a normal renewing epithelium such as the intestine exhibits a DNA replication index of approximately 16% (29). Furthermore, individuals carrying an extra copy of chromosome 21 have a 50% lower probability of developing solid tumors than individuals with the correct chromosome number (21,22). Segmental trisomy in the mouse has been shown to reduce incidence of neoplasia in the sensitized APC Min genetic background (26).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this idea is the observation that the occurrence of acute lymphoblastic leukemia and acute megakaryoblastic leukemia is greatly increased in Down Syndrome patients (20). However, the incidence of many solid tumors in these individuals is only half of that in the normal population, raising the possibility that aneuploidy also restricts the formation of certain tumors (21,22). Studies of mouse mutants that result in an increased frequency of aneuploidy also revealed mixed results.…”

Section: Effects Of Trisomy On Immortalizationmentioning

confidence: 95%

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Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

Williams

Prabhu

Hunter

et al. 2008

Science

559

601

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Aneuploidy, an incorrect chromosome number, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional copy of certain chromosomes. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Trisomy On Immortalizationmentioning

confidence: 95%

Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

Williams

Prabhu

Hunter

et al. 2008

Science

559

601

View full text Add to dashboard Cite

show abstract

“…Interestingly, when the proportion of tumours in the paediatric age group was compared between different tissue types in Denmark 23 , France 34 and the European Union 35 , a strikingly skewed picture emerged, especially for neuroblastomas and for tumours of the central nervous system (CNS; considered as one group): for the Danish and French studies the expected incidence was 30% and 45% but the observed incidence was 1% and 0% in DS children, respectively 23,34 . The relative abundance of Wilms' tumour is also substantially reduced 23,34 .…”

Section: Skewed Profile Of Paediatric Tumours In Dsmentioning

confidence: 94%

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

2012

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If assessed by a number of criteria for cancer predisposition, Down's syndrome (DS) should be an overwhelmingly cancer-prone condition. Although childhood leukaemias occur more frequently in DS, paradoxically, individuals with DS have a markedly lower incidence of most solid tumours. Understanding the mechanisms that are capable of overcoming such odds could potentially open new routes for cancer prevention and therapy. In this Opinion article, we discuss recent reports that suggest unique and only partially understood mechanisms behind this paradox, including tumour repression, anti-angiogenic effects and stem cell ageing and availability.

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“…Several lines of evidence indicate that aneuploidy suppresses rather than promotes tumorigenesis. First, individuals carrying an extra copy of chromosome 21 have a 50% lower probability of developing solid tumors than individuals with the correct chromosome number (Hasle et al 2000;Satge et al 2003). Second, mice carrying segmental trisomies exhibit a reduced incidence of neoplasia in the sensitized apc Min genetic background (Sussan et al 2008).…”

Section: Why Are Most Tumors Aneuploid?mentioning

confidence: 99%

Aneuploidy: Cells Losing Their Balance

2008

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A change in chromosome number that is not the exact multiple of the haploid karyotype is known as aneuploidy. This condition interferes with growth and development of an organism and is a common characteristic of solid tumors. Here, we review the history of studies on aneuploidy and summarize some of its major characteristics. We will then discuss the molecular basis for the defects caused by aneuploidy and end with speculations as to whether and how aneuploidy, despite its deleterious effects on organismal and cellular fitness, contributes to tumorigenesis.

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Are solid tumours different in children with Down's syndrome?

Cited by 22 publications

References 10 publications

Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

Aneuploidy: Cells Losing Their Balance

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