Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH

Caselli, Rossella; Speciale, Caterina; Pescucci, Chiara; Uliana, Vera; Sampieri, Katia; Bruttini, Mirella; Longo, Ilaria; Francesco, Sonia De; Pramparo, Tiziano; Zuffardi, Orsetta; Frezzotti, R.; Acquaviva, Antonio; Hadjistilianou, Theodora; Renieri, Alessandra; Mari, Francesca

doi:10.1007/s10038-007-0151-4

Cited by 20 publications

(21 citation statements)

References 20 publications

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“…A distinct facial phenotype has been described for retinoblastoma patients bearing a deletion of 13q14 [Baud et al, 1999;Bojinova et al, 2001;Caselli et al, 2007] including broad forehead, prominent philtrum, thick anteverted ear lobes, and a thick lower lip. Our patient has some of these features, particularly the prominent forehead and thick lower lip, but he also had other features not described in typical retinoblastoma patients.…”

Section: Discussionmentioning

confidence: 98%

Interstitial deletion of 13q associated with polymicrogyria

Kogan

Egelhoff

Saal

2008

American J of Med Genetics Pt A

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Interstitial deletion of the long arm of chromosome 13 is a rare condition characterized by multiple clinical findings. We report a male dizygotic twin with an interstitial deletion of 13q and failure to thrive, hypotonia, polymicrogyria, bilateral foci of retinoblastoma, hearing loss, bilateral inguinal hernias, submucous cleft palate, and dysmorphic features including a triangular shaped face, broad forehead, small chin, prominent eyes, downslanting palpebral fissures, and a downturned mouth. Chromosome analysis showed an interstitial deletion of chromosome 13 which was confirmed by fluorescence in situ hybridization analysis to include the Rb locus, but spare the 13q subtelomeric region. The karyotype was 46,XY,del(13)(q14.1q31.2).ish del(13)(RB1-,D13S327+) de novo. Breakpoints were further characterized by SNP-based microarray. Retinoblastoma tumors are a well-known complication of deletion of the retinoblastoma susceptibility gene, located at chromosome 13q14.2. Growth retardation is another common feature that has been described in other patients with a deletion of 13q. Additionally, this patient had brain findings on MRI consistent with bilateral polymicrogyria with predominance of the frontal lobes, as well as prominent infratentorial and supratentorial vasculature. There are a variety of polymicrogyria syndromes that are distinguished by the cortical location of the abnormal folding. Several of the subtypes have known genetic loci associated with them. To our knowledge, this is the only report of polymicrogyria in association with a deletion of chromosome 13.

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Section: Discussionmentioning

confidence: 98%

Interstitial deletion of 13q associated with polymicrogyria

Kogan

Egelhoff

Saal

2008

American J of Med Genetics Pt A

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“…However, little is known about their roles in cancers. Protocadherins are predominantly expressed during development of the nervous system, and their functions could be related to the differentiation of embryonic cells [18–20]. Repression of protocadherin expression might contribute to tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Protocadherin 17 functions as a tumor suppressor suppressing Wnt/β-catenin signaling and cell metastasis and is frequently methylated in breast cancer

Yin

Xiang

et al. 2016

Oncotarget

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Protocadherins play important roles in the regulation of cell adhesion and signaling transduction. Aberrant expression of protocadherins has been shown to be associated with multiple tumorigenesis. We previously identified PCDH17, encoding protocadherin 17, as a frequently methylated and downregulated tumor suppressor gene (TSG) in gastric and colorectal cancers. Here, we examined the abnormalities and functions of PCDH17 in breast cancer pathogenesis. We used PCR and immunohistochemistry to check its expression pattern in breast tumor cell lines and primary tumors. Methylation-specific PCR (MSP) was applied to examine its promoter methylation status in breast tumor cell lines and primary tumors. The biological functions of PCDH17 in breast tumor cells were assessed using in vitro and in vivo assays. We found that PCDH17 was frequently downregulated or silenced in 78% (7/9) of breast tumor cell lines, as well as 89% (32/36) of primary tumors. Downregulation of PCDH17 in breast cancer was mainly due to the methylation of its promoter. Ectopic expression of PCDH17 in breast tumor cells inhibited cell proliferation and mobility through arresting cell cycle and inducing apoptosis. In breast tumor cells, PCDH17 significantly suppressed the active β-catenin level and its downstream target gene expression. Thus, we found that PCDH17 functions as a tumor suppressor inhibiting Wnt/β-catenin signaling and metastasis in breast cancer but is frequently methylated in primary tumors which could be a potential biomarker.

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“…Neurological abnormality in patients with deletions in NUFIP1 suggests its important role in normal neuron development [50,51]. Of note, both ATRX and NUFIP1 physically interacts with BRCA1 [48,52], suggesting their possible functions in the same protein complex.…”

Section: Discussionmentioning

confidence: 99%

Massively Parallel Sequencing Reveals an Accumulation of De Novo Mutations and an Activating Mutation of LPAR1 in a Patient with Metastatic Neuroblastoma

et al. 2013

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Neuroblastoma is one of the most genomically heterogeneous childhood malignances studied to date, and the molecular events that occur during the course of the disease are not fully understood. Genomic studies in neuroblastoma have showed only a few recurrent mutations and a low somatic mutation burden. However, none of these studies has examined the mutations arising during the course of disease, nor have they systemically examined the expression of mutant genes. Here we performed genomic analyses on tumors taken during a 3.5 years disease course from a neuroblastoma patient (bone marrow biopsy at diagnosis, adrenal primary tumor taken at surgical resection, and a liver metastasis at autopsy). Whole genome sequencing of the index liver metastasis identified 44 non-synonymous somatic mutations in 42 genes (0.85 mutation/MB) and a large hemizygous deletion in the ATRX gene which has been recently reported in neuroblastoma. Of these 45 somatic alterations, 15 were also detected in the primary tumor and bone marrow biopsy, while the other 30 were unique to the index tumor, indicating accumulation of de novo mutations during therapy. Furthermore, transcriptome sequencing on the 3 tumors demonstrated only 3 out of the 15 commonly mutated genes (LPAR1, GATA2, and NUFIP1) had high level of expression of the mutant alleles, suggesting potential oncogenic driver roles of these mutated genes. Among them, the druggable G-protein coupled receptor LPAR1 was highly expressed in all tumors. Cells expressing the LPAR1 R163W mutant demonstrated a significantly increased motility through elevated Rho signaling, but had no effect on growth. Therefore, this study highlights the need for multiple biopsies and sequencing during progression of a cancer and combinatorial DNA and RNA sequencing approach for systematic identification of expressed driver mutations.

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Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH

Cited by 20 publications

References 20 publications

Interstitial deletion of 13q associated with polymicrogyria

Interstitial deletion of 13q associated with polymicrogyria

Protocadherin 17 functions as a tumor suppressor suppressing Wnt/β-catenin signaling and cell metastasis and is frequently methylated in breast cancer

Massively Parallel Sequencing Reveals an Accumulation of De Novo Mutations and an Activating Mutation of LPAR1 in a Patient with Metastatic Neuroblastoma

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