Identification of five new families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutations

Krutilkova, Vera; Trková, Marie; Fleitz, Julie; Vladimir, Guţu; Novotna, Kamila; Křepelová, Anna; Sumerauer, David; Kodet, Roman; Širůčková, Simona; Plevová, Pavlína; Bendová, Šárka; Hedvičáková, Petra; Foreman, Nicholas K.; Sedláček, Zdeněk

doi:10.1016/j.ejca.2005.01.026

Cited by 89 publications

(46 citation statements)

References 25 publications

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“…These tumour types belong to the typical tumour spectrum of heterozygous p53 mutant mice (Donehower et al, 1992), and the strong oncogenic synergy between Nf2 and p53 inactivation in mice is well established (McClatchey et al, 1998;Robanus-Maandag et al, 2004). In contrast, the choroid plexus hypertrophy and carcinoma are likely related to p53 rather than Nf2 loss, as choroid plexus tumours are frequently observed in the context of the Li-Fraumeni (TP53) inherited cancer syndrome (Krutilkova et al, 2005). In contrast, the survival of PGDSCre; Nf2 flox2/À ;p16 ink4aÀ/À mice was similar to that of PGDSCre;Nf2 flox2/À mice.…”

Section: Resultsmentioning

confidence: 99%

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

et al. 2011

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Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) ( þ ) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS ( þ ) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation.

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Section: Resultsmentioning

confidence: 99%

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

et al. 2011

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“…Diagnosis of a choroid plexus carcinoma in a cancer-prone family might therefore justify TP53 mutational screening in the context of careful human genetic counseling (Krutilkova et al, 2005;Gonzalez et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Novel oncogene amplifications in tumors from a family with Li–Fraumeni syndrome

Remke

Hartmann

Korshunov

et al. 2009

Genes Chromosomes & Cancer

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Li-Fraumeni syndrome (LFS) represents an inherited tumor syndrome that is typically caused by germline mutations of the tumor suppressor gene TP53. TP53 dysfunction secondarily disturbs the genetic integrity of the cell. Here, we report a family with LFS harboring a germline TP53 mutation (R248W) located in the functional domain of the protein that binds to the minor groove of the DNA. In this family, tumors of the central nervous system were diagnosed as primary malignancies in all carriers of the mutation. The index patient developed an anaplastic medulloblastoma with unusual genomic profile exhibiting six distinct high-level genomic amplifications, two of them targeting the MYCN and GLI2 genes, respectively. In an extrarenal rhabdoid tumor from the same patient, we found a novel high-level amplification of the MYC oncogene. The father of this patient was diagnosed with myxopapillary ependymoma (WHO degrees I), whereas a brother died from an early relapse of a choroid plexus carcinoma. The analysis of this LFS familiy thus revealed novel oncogene amplifications as different second hits that are likely to also play a role in the pathogenesis of their sporadic counterparts.

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“…Since their 3 cases, there have been 17 additional cases, including this report, of primary CPC, occurring in patients with LFS/LFL, germline TP53 mutations, or both [12, 13, 15, 29,45,46,47,48,49,50]. The number of such cases may be underestimated since many reports do not distinguish between types of CNS tumors or divide CPTs into papillomas and carcinomas [1,2,3,4,5, 23, 25, 26, 51, 52].…”

Section: Discussionmentioning

confidence: 99%

“…Primary choroid plexus carcinoma (CPC) in childhood has sporadically been associated with the LFSs [12,13,14,15]. We describe here a new TP53 germline mutation arising in an LFS family with a proband who was an infant when diagnosed with a primary CPC, a half-sibling who died of primary leptomeningeal sarcomatosis as an infant, and a paternal grandmother diagnosed with multiple malignancies before 45 years of age, including breast cancer [16].…”

Section: Introductionmentioning

confidence: 99%

A Novel <i>TP53</i> Germline Mutation in a Family with a History of Multiple Malignancies: Case Report and Review of the Literature

Agarwalla

Dunn²,

Turner³

et al. 2008

Pediatr Neurosurg

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Objective: Choroid plexus carcinoma (CPC) has been associated with TP53 germline mutations and Li-Fraumeni syndrome (LFS). We describe our finding of a novel germline mutation in the TP53 gene in a family with multiple malignancies and in association with a child presenting with CPC. Method: An 8-month-old male presented with seizure-like activity; imaging disclosed a 1.5-cm left ventricular mass confirmed to be CPC intra- and postoperatively. Family history was significant for a half-sister who died of a primary CNS sarcoma and a paternal grandmother negative for BRCA1, BRCA2, MLH1, and MSH2 mutations with multiple (>6) LFS spectrum malignancies. Results: Familial TP53 testing revealed an A→T substitution at DNA position 13071, creating a deleterious Asn→Ile substitution at amino acid 131 in exon 5. Conclusion: Physicians treating patients with CPC should be attuned to reviewing family history for risk factors suggestive of genetic cancer syndromes such as LFS. These syndromes markedly influence both the patient and family members and may alter postoperative treatment regimens.

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Identification of five new families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutations

Cited by 89 publications

References 25 publications

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

Novel oncogene amplifications in tumors from a family with Li–Fraumeni syndrome

A Novel <i>TP53</i> Germline Mutation in a Family with a History of Multiple Malignancies: Case Report and Review of the Literature

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