Rhabdomyosarcoma, Wilms tumor, and deletion of the patched gene in Gorlin syndrome

Cajaíba, Mariana M.; Bale, Allen E.; Alvarez-Franco, Mayra; McNamara, Joseph E.; Reyes‐Múgica, Miguel

doi:10.1038/ncponc0608

Cited by 41 publications

(40 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Wilms tumor, which is rare, was previously reported in four patients with NBCCS and constitutional 9q22.3 microdeletion [Cajaiba et al, 2006;Isidor et al, 2013]; the hyper-expression of IGF2 is often present in sporadic Wilms tumours and has been suggested as the pathogenetic mechanism for the development of Wilms tumors in rare cases of NBCCS, as PTCH1 downgrades the expression of IGF2 [Hahn et al, 1998[Hahn et al, , 2000Anderson et al, 1999;Hartmann et al, 2005;Cajaiba et al, 2006]. What has clearly emerged is that patients affected with 9q22.3 microdeletion run a higher risk of Wilms tumor.…”

Section: Discussionmentioning

confidence: 99%

“…So far 37 patients have been reported as being diagnosed with 9q22 deletions that either matched clinical criteria as regards diagnosis of NBCCS or include PTCH1 within the deleted interval, not including intragenic deletions [Sekhon et al, 1982;Ying et al, 1982;Farrell et al, 1991;Robb et al, 1991;Evans et al, 1993;Kroes et al, 1994;Shimkets et al, 1996;Paoloni-Giacobino et al, 2000;L'Hermine et al, 2002;Olivieri et al, 2003;Haniffa et al, 2004;Midro et al, 2004;Boonen et al, 2005;Cajaiba et al, 2006;Chen et al, 2006;Redon et al, 2006;Fujii et al, 2007;Nowakowska et al, 2007;de Ravel et al, 2009;Musani et al, 2009;Shimojima et al, 2009;Yamamoto et al, 2009;Muller et al, 2012]. Several of the patients presented craniosynostosis, severe obstructive hydrocephalus, macrosomia, and developmental delay, which are not usually seen in NBCCS.…”

Section: Discussionmentioning

confidence: 99%

“…Other tumors which were reported include rhabdomyoma, lymphoma, thyroid adenoma, and meningioma [Cajaiba et al, 2006;Evans et al, 2002]. The literature is scarce regarding other kind of tumors, which can occur in this condition.…”

Section: Discussionmentioning

confidence: 99%

“…The risk of other malignant tumors is evidently not greater, but lymphoma and meningioma have been detected [Evans and Farndon, 2002]. The literature is sparse regarding other kinds of tumors, which can occur in this condition.Wilms tumor has only ever been mentioned in the literature in four patients [Cajaiba et al, 2006;Isidor et al, 2013]. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 trough 9q31.1 that includes the entire codifying sequence of the gene PTCH, with Wilms tumor, multiple kinds of tumors (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid, adenomatoid tumor of the pleura, parathyroid adenoma) and a severe clinical presentation.…”

mentioning

confidence: 96%

See 3 more Smart Citations

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci

Garavelli¹,

Piemontese

Cavazza

et al. 2013

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS. 2894 INTRODUCTIONGorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) also known as basal cell nevus syndrome (BCNS, OMIM #109400) is an autosomal dominant condition due to haploinsufficiency of PTCH1 and mainly characterized by the development of mandibular keratocysts which often have their onset during adolescence and/or multiple basal cell carcinomas normally arising after age 20 [Hahn et al., 1996;Evans and Farndon, 2002;Gorlin, 2004;Muzio et al., 2013]. Exonic, multiexonic, and whole-gene deletions have been reported in about 6% of individuals with NBCCS [Evans and Farndon, 2002]. The studies of disease prevalence come from the UK population, where it is nearer to 1:30,827 [Evans et al., 2010]; The actual figure could be higher still, since less severe cases may not be diagnosed and Jones et al. [2011] recently reported an incidence of 1 in 19,000 births.NBCCS is clinically diagnosed in patients with one major diagnostic criterion and molecular confirmation or two major criteria or one major and two minor diagnostic criteria [Bree et al., 2011]. The major criteria are the following: (1) BCC before the age of 20 or excessive numbers of BBCs out of proportion to prior sun exposure and skin type, (2) odontogenic jaw keratocyst prior to 20 years of age, (3) palmar or plantar pitting, (4) lamellar calcification of the falx cerebri, (5) medulloblastoma typically desmoplastic, and (6) first-degree relative with NBCCS. The minor criteria are the following: (1) rib anomalies, (2) other specific skeletal malformations and radiologic changes (i.e., vertebral anomalies, kyphoscoliosis, short fourth metacarpals, postaxial polydactyly), (3) macrocephaly, (4) cleft lip/palate, (5) ovarian/ cardiac fibromas, (6) lymphomesenteric cysts, and (7) ocular anomalies including the following: strabismus, hypertelorism, congenital cataract, glaucoma, coloboma.The typical facial phenotype includes macrocephaly, frontal bossing, coarse face ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

See 2 more Smart Citations

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci

Garavelli¹,

Piemontese

Cavazza

et al. 2013

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Among all previously published patients, only one patient developed malignancies including nephroblastoma. 11 The three patients described in this study raise to 4/30 the number of patients with 9q22.3 microdeletion and nephroblastoma.…”

Section: Discussionmentioning

confidence: 99%

Wilms’ tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas

et al. 2012

View full text Add to dashboard Cite

Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth syndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 gene. Subsequently, we identified a somatic PTCH1 nonsense mutation in the renal tumor of one patient. In addition, by array comparative genomic hybridization method, we analyzed the DNA extracted from the blood samples of nine patients with overgrowth syndrome and WT, but did not identify any deleterious chromosomal imbalances in these patients. These findings strongly suggest that patients with constitutional 9q22.3 microdeletion have an increased risk of WT, and that PTCH1 have a role in the pathogenesis of nephroblastomas.

show abstract

Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay

Muller

Aradhya²,

Atkin

et al. 2011

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1. With the availability of comparative genomic hybridization arrays, increasing numbers of individuals with microdeletions involving this locus are being identified. We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352 kb to 20.5 Mb in size, the largest spanning 9q21.33 through 9q31.2. There was significant overlap of the deleted segments among most of the patients. The smallest common regions shared among the deletions were identified in order to localize putative candidate genes that are potentially responsible for each of the non-BCNS features. These were a 929 kb region for metopic craniosynostosis, a 1.08 Mb region for obstructive hydrocephalus, and a 1.84 Mb region for macrosomia. Additional studies are needed to further characterize the candidate genes within these regions.

show abstract

Rhabdomyosarcoma, Wilms tumor, and deletion of the patched gene in Gorlin syndrome

Abstract: Left nephrectomy, excision of paravesical tumor, excision of mandibular cysts, chemotherapy, and radiotherapy.

Cited by 41 publications

References 18 publications

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci

Wilms’ tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas

Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay

Contact Info

Product

Resources

About