Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (<i>PTCH1)</i> and Suppressor of fused (<i>SUFU)</i><i>SUFU</i> mutation carriers appear to have an especially high risk of early-onset medulloblastoma.
|
28620006 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
By combining SB mutagenesis with Patched1 heterozygous mice (Ptch1(lacZ/+)), we observed an increased frequency of MB and decreased tumor-free survival compared with Ptch1(lacZ/+) controls.
|
24167280 |
2013 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
In several of these cases, activation of HH-GLI signaling is mediated by overproduction of HH ligands (e.g., prostate cancer), loss-of-function mutations in <i>PTCH1</i> or gain-of-function mutations in <i>SMO</i>, which occur in the majority of basal cell carcinoma (BCC), SHH-subtype medulloblastoma and rhabdomyosarcoma.
|
31244888 |
2019 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma.
|
21188540 |
2011 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
It now appears that constitutive activation of Hedgehog signalling, by inactivating mutations in PTCH1 or activating mutations in the coreceptor SMOH, is required and possibly sufficient for basal cell carcinoma development and also contributes to the formation of a variety of other tumour types, including medulloblastoma and rhabdomyosarcoma.
|
11130178 |
2000 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Ptc1(+/-) mice develop spontaneous rhabdomyosarcoma (RMS) and medulloblastoma (MB), as well as BCC following radiation exposure.
|
15925443 |
2006 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
In addition, Trim32 knockout enhances the incidence of medulloblastoma (MB) formation in the Ptch1 mutant mice.
|
31527798 |
2020 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Constitutive activation of hedgehog signaling, often caused by PTCH1 inactivation and leading to inappropriate activation of GLI target genes, is crucial for the development of several human tumors including basal cell carcinoma of the skin and medulloblastoma.
|
15521068 |
2005 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997.
|
10375116 |
1999 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
CTD_human |
Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice.
|
19155313 |
2009 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Significantly, loss of MDM2 in Ptch1(+/-) mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis.
|
21437245 |
2011 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Using Ptch1(+/-) mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH) is an early event that is associated with high levels of cell senescence in preneoplasia.
|
26997276 |
2016 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
In mice, Ptc1 haploinsufficiency and disruption of DNA repair (DNA ligase IV inactivation) or cell cycle regulation (Kip1, Ink4d, or Ink4c inactivation), in conjunction with p53 dysfunction, predispose to medulloblastoma.
|
14500378 |
2003 |
Childhood Medulloblastoma
|
0.400 |
PosttranslationalModification
|
disease |
BEFREE |
Whereas genetic mutations in PTCH1 have previously been shown to lead to medulloblastoma, our study indicates that epigenetic silencing of PTCH1, and other critical developmental loci, by DNA methylation is a fundamental process of pediatric medulloblastoma formation.
|
19966297 |
2010 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression.<i></i>.
|
28986380 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Simultaneous deletion of Zfx along with Ptch1 prevented BCC formation and delayed medulloblastoma development.
|
25164012 |
2014 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
In contrast, mice lacking one or two functional Ink4c alleles and one copy of Patched (Ptc1) encoding the Shh receptor rapidly developed MBs that retained wild-type p53.
|
16260494 |
2005 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Novel PTCH1 mutations in Japanese Nevoid basal cell carcinoma syndrome patients: two familial and three sporadic cases including the first Japanese patient with medulloblastoma.
|
21368767 |
2011 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Whereas Gorlin's syndrome patients carry germ-line mutations in the patched (PTCH) gene, Turcot's syndrome patients with MBs carry germ-line mutations of the adenomatous polyposis coli (APC) gene.
|
11585731 |
2001 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors.
|
26935062 |
2017 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Patched1 heterozygous (Ptch1 <sup>+/-</sup>) mice, carrying a germ-line heterozygous inactivating mutation in the Ptch1 gene, the Shh receptor and negative regulator of the pathway, are uniquely susceptible to MB development after radiation damage in neonatal cerebellum.
|
29079783 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Here we use a mouse model of Ptch1 heterozygosity to reveal a critical tumor suppressor function for Hic1 in medulloblastoma.
|
18347096 |
2008 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Conversely, patients with PTCH1 germline mutations experience Shh overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) syndrome and an increased incidence of malignant transformation of CGNPs leading to medulloblastoma formation.
|
27444290 |
2016 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Finally, compound 24 led to significant regression of subcutaneous tumor generated by primary Ptch1-deficient medulloblastoma cells in SCID mouse.
|
28618224 |
2017 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P(combined) < 0.05).
|
26290144 |
2015 |