ライフサイエンスコーパス: BWS

1 BWS is thought to involve one or more imprinted genes, s

2 BWS patients enrolled onto NWTS 4 had smaller tumors tha

3 BWS patients were more likely to present with lower-stag

4 though SSCP analysis of 62 WT samples and 10 BWS patients did not result in the identification of any

5 II (IGF2), which was found in 2 of 10 (20%) BWS patients, even though LOI of IGF2 occurs frequently

6 Similarly, 21 of 36 (58%) BWS patients showed loss of maternal allele-specific met

7 ese associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G alle

8 These data suggest that KIP2 is a BWS gene but that it is not uniquely equivalent to the 1

9 was abrogated in TGF-beta-defective mice and BWS, resulting in TERT overexpression.

10 amine their expression pattern in tumors and BWS patients, since epigenetic alteration at these loci

11 in some cases, altered imprinting in WT and BWS.

12 eristics and outcome of patients with WT and BWS.

13 n cancer and in epigenetic syndromes such as BWS and skewed X-inactivation.

14 Both BWS and LOS involve misregulation of imprinted genes.

15 ix of 149 cases were reported from a British BWS registry; the same numbers were recorded in a French

16 ons, in any of these suppressors could cause BWS.

17 en inherited maternally, the deletion causes BWS with silencing of p57(KIP2), indicating deletion of

18 lated, genes, we generated a mouse model for BWS that both harbors a null mutation in p57(Kip2) and d

19 ) mice provide an important animal model for BWS, as well as sporadic cancers associated with it, inc

20 hway and is responsible at least in part for BWS-associated tumorigenesis as well as sporadic human c

21 uggesting that Kvlqt1 is not responsible for BWS.

22 By positional cloning from BWS breakpoints, we have isolated a gene 100 kb and 65 k

23 TERT) were overexpressed in fibroblasts from BWS patients and TGF-beta-defective mice.

24 ch enrolled patient, whether the patient had BWS.

25 lled onto NWTS 3 and 4 were reported to have BWS.

26 manner, a finding that may help explain how BWS can arise from mutations in either gene.

27 SP is a new potential causal factor in human BWS patients.

28 most common constitutional abnormalities in BWS are epigenetic, involving abnormal methylation of ei

29 IT1 is the most common genetic alteration in BWS.

30 P2), alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterat

31 s, translocations, or methylation defects in BWS have so far been found in three of the linked matern

32 S; however, a role of TGF-beta deficiency in BWS-associated neoplastic transformation is unexplored.

33 date the only genetic mutations described in BWS are in the CDKN1C gene.

34 suppressing functions that are disrupted in BWS and embryonal tumors.

35 locus in LOS, the most common epimutation in BWS.

36 in conformations are differently favoured in BWS and SRS likely predisposing the locus to the activat

37 ions and CTCF--cohesin binding at the ICR in BWS and SRS together with DNA methylation correlate with

38 ated by CTCF, and this regulation is lost in BWS, leading to aberrant overexpression of growth-promot

39 t the hypothesis that loss of methylation in BWS patients activates the repressive function of KvDMR1

40 many phenotypic characteristics observed in BWS patients, suggesting that beta2SP mutant mice phenoc

41 g of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of

42 ld be associated with specific phenotypes in BWS.

43 s disrupted by chromosomal rearrangements in BWS patients, as well as by a balanced chromosomal trans

44 ion of the importance of this gene region in BWS.

45 ine an epigenotype-phenotype relationship in BWS, in which aberrant methylation of H19 and LIT1 and U

46 We further show that in BWS and SRS cells, there is opposing chromatin looping c

47 Although p57KIP2 was undetectable in BWS tongue, similar results were also observed in postna

48 Eight of sixteen informative BWS patients (50%) showed biallelic expression, i.e., lo

49 that LOS is a multilocus LOI syndrome, as is BWS.

50 We previously mapped BWS, by genetic linkage analysis, to 11p15.5, which we a

51 and characterized a mouse model that mimics BWS microdeletions to define the role of the deleted seq

52 st within the KvLQT1 locus, because multiple BWS-associated chromosome rearrangements disrupt this ge

53 d showed biallelic expression in one of nine BWS patients studied.

54 ly reported to show mutations in two of nine BWS patients.

55 results were also observed in postnatal non-BWS tongue samples.

56 NWTS 3 (P =.02), a trend not seen in the non-BWS patients.

57 Approximately 20% of BWS cases have uniparental disomy (UPD) of chromosome 11

58 ific expression and/or methylation in 20% of BWS patients, and p57KIP2, a cyclin-dependent kinase inh

59 st or lymphocyte DNA; whereas, in 4 cases of BWS with H19 hypermethylation, methylation at KvDMRl was

60 Among 12 cases of BWS with normal H19 methylation, 5 showed demethylation

61 ain of the KIP2 gene in one of five cases of BWS.

62 mice display many of the characteristics of BWS, including placentomegaly and dysplasia, kidney dysp

63 Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57KIP2.

64 l silencing of CDKN1C and the development of BWS.

65 Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

66 l allele may cause at least some features of BWS.

67 c characteristics of the most common form of BWS, including loss of methylation at KvDMR1 and biallel

68 The genetics of BWS have implicated a gene that maps to chromosome 11p15

69 ollow muscle development in a mouse model of BWS to dissect the separate and shared roles for misexpr

70 al characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS.

71 addition, the precise phenotypic spectrum of BWS might depend on which maternally expressed gene is m

72 A subset of BWS patients has been identified with loss-of-function m

73 f IGF2 can result in most of the symptoms of BWS.

74 that are phenotypically similar to those of BWS patients.

75 However, one BWS patient did show LOI of p57KIP2 in skin fibroblasts.

76 uggesting that beta2SP mutant mice phenocopy BWS, and beta2SP loss could be one of the mechanisms ass

77 hat the maternal allele is disrupted in rare BWS patients with balanced germ-line chromosomal rearran

78 gh KvDMR1 may be an underlying cause of some BWS cases.

79 In sporadic BWS cases the majority of patients have epimutations in

80 DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the

81 t angles; the amount of body weight support (BWS); and lower limb loading.

82 nting disorders Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS).

83 owth disorders, Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS).

84 in the region, Beckwith-Wiedemann syndrome (BWS) and Wilms tumor are each associated with loss of ma

85 mental disorder Beckwith Wiedemann Syndrome (BWS) and with several cancers.

86 Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms' tumor (

87 m patients with Beckwith-Wiedemann syndrome (BWS) have been mapped to 11p15.5 between p57KIP2 and IGF

88 gh incidence of Beckwith-Wiedemann syndrome (BWS) in children conceived with ARTs.

89 Beckwith-Wiedemann syndrome (BWS) is a clinically variable disorder characterized by

90 Beckwith-Wiedemann syndrome (BWS) is a congenital cancer-predisposition syndrome asso

91 Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregu

92 Beckwith-Wiedemann syndrome (BWS) is a hereditary human cancer stem cell syndrome cur

93 Beckwith-Wiedemann syndrome (BWS) is a human stem cell disorder, and individuals with

94 Beckwith-Wiedemann syndrome (BWS) is a model human imprinting disorder resulting from

95 Beckwith-Wiedemann syndrome (BWS) is an autosomal dominant disorder of increased pren

96 The Beckwith-Wiedemann syndrome (BWS) is genetically linked to chromosome 11p15.5, and a

97 The Beckwith-Wiedemann syndrome (BWS) is marked by fetal organ overgrowth and conveys a p

98 o the imprinted Beckwith-Wiedemann syndrome (BWS) locus at 11p15.5.

99 e human disease Beckwith-Wiedemann syndrome (BWS) may disrupt CDKN1C expression.

100 drome (PWS) and Beckwith-Wiedemann Syndrome (BWS) where imprinting is known to be a contributing fact

101 m patients with Beckwith-Wiedemann syndrome (BWS), a condition characterized by prenatal overgrowth a

102 ases, including Beckwith-Wiedemann syndrome (BWS), a disorder of prenatal overgrowth and predispositi

103 s with sporadic Beckwith-Wiedemann syndrome (BWS), a fetal overgrowth syndrome associated with an imp

104 features of the Beckwith-Wiedemann syndrome (BWS), a genetically complex human disorder associated wi

105 inting leads to Beckwith-Wiedemann syndrome (BWS), an overgrowth and cancer predisposition condition.

106 n patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer.

107 Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth, midline abdomina

108 tal disorder is Beckwith-Wiedemann syndrome (BWS), which increases risk for embryonal cancers, includ

109 Beckwith-Wiedemann syndrome (BWS), which predisposes to cancer and excessive growth,

110 f patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of I

111 ition condition Beckwith-Wiedemann syndrome (BWS).

112 t tumors and in Beckwith-Wiedemann syndrome (BWS).

113 rowth syndrome, Beckwith-Wiedemann syndrome (BWS).

114 er-predisposing Beckwith-Wiedemann syndrome (BWS).

115 sorders such as Beckwith-Wiedemann syndrome (BWS).

116 yndrome-namely, Beckwith-Wiedemann syndrome (BWS).

117 human disease, Beckwith--Wiedemann syndrome (BWS).

118 ith chromosomal rearrangements, suggest that BWS can involve disruption of multiple independent 11p15

119 The BWS mutation was an in-frame three-amino-acid deletion t

120 band that encompassed the ABCC8 gene and the BWS locus.

121 auses deregulation of imprinted genes at the BWS locus on 11p15.5.

122 The overall treatment outcomes for the BWS patients were nearly identical to those without BWS,

123 K9me3 and H4K20me3 becoming biallelic in the BWS and H3K4me2, H3K27me3 and H3K9ac together with CTCF-

124 ge to the Beckwith-Weidemann syndrome of the BWS region on the short arm of chromosome 11.

125 we performed a case-cohort study, using the BWS Registry.

126 Therefore, BWS in humans may result from disruption of appropriate

127 5 kb centromeric to the proximal end of this BWS breakpoint cluster and p57KIP2, respectively.

128 In contrast to BWS and Wilms tumor, these syndromes do not show any par

129 screen for other genetic predispositions to BWS, the conserved sequences between human and mouse dif

130 n-exon boundaries of p57KIP2 in 40 unrelated BWS patients.

131 the overgrowth syndrome Beckwith-Wiedemann (BWS).

132 LOI) overgrowth syndrome Beckwith-Wiedemann (BWS).

133 The only known mutations associated with BWS are maternally transmitted translocations, which are

134 ional epigenetic alterations associated with BWS have been well characterized and include epigenetic

135 ansmission of hIC1 mutations associated with BWS in mice.

136 cific epigenetic alterations associated with BWS-four at LIT1 and one at both LIT1 and H19.

137 uld be one of the mechanisms associated with BWS.

138 -beta signaling, is causally associated with BWS; however, a role of TGF-beta deficiency in BWS-assoc

139 We analyzed a cohort of 52 children with BWS and UPD using a panel of microsatellite markers for

140 ly lower than the frequency in children with BWS and Wilms tumor, 79% (11/14; P = .0028).

141 nal epigenotypes from those of children with BWS and Wilms tumor.

142 Like children without BWS, children with BWS and WT have an excellent prognosis with modern treat

143 A total of seven children with BWS were born after ART-five of whom were conceived afte

144 ng phenotypically, but not genetically, with BWS.

145 One third of individuals with BWS lose maternal-specific methylation at KvDMR1, a puta

146 In the majority of individuals with BWS, maternal-specific methylation at KvDMR1 is absent a

147 Other studies associate KVLQT1 with BWS.

148 The cohort consisted of 92 patients with BWS and molecular analysis of both H19 and LIT1, and the

149 Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of

150 t, and that in the majority of patients with BWS, LIT1 is abnormally expressed from both the paternal

151 and other tumors, and in some patients with BWS.

152 Like children without BWS, children with BWS and WT have an excellent prognosi

153 ients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at

154 ients compared with patients with WT without BWS.