High Frequency of Germline <i>SUFU</i> Mutations in Children With Desmoplastic/Nodular Medulloblastoma Younger Than 3 Years of Age

Brugières, Laurence; Remenieras, Audrey; Pierron, Gaëlle; Varlet, Pascale; Forget, Sébastien; Byrde, Véronique; Bombled, Johny; Puget, Stéphanie; Caron, Olivier; Dufour, Christelle; Delattre, Olivier; Paillerets, Brigitte Bressac-de; Grill, Jacques

doi:10.1200/jco.2011.38.7258

Cited by 107 publications

(99 citation statements)

References 23 publications

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“…The third observation is the multiplicity of rare events that are typically accumulated before a malignant population is detectable (2,23,(50)(51)(52). The fact that these events are rare is supported by the many years found to separate the first events and the appearance of a derivative malignant cell population (53,54). However, unless an initial change deregulates cell output, the clone it produces is unlikely to comprise sufficient progeny to ensure that at least one undergoes a further compounding change.…”

Section: Normal Neoplastic and Cancer Scsmentioning

confidence: 99%

Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications

et al. 2013

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Accumulating evidence suggests that human cancers develop through a step-wise, but nonlinear process of cellular diversification and evolution. Recent mutational analyses indicate that this process is more complex and diverse than anticipated before whole-genome sequencing methods were readily available. Examples are also emerging now of genetically abnormal clones of cells that have acquired mutations with known oncogenic potential but, nevertheless, may show no manifestations of malignant change for many years. To accommodate these diverse realities, we suggest the term neoplastic refer to clones of cells that have any type of somatic aberrancy associated with an increased propensity to become malignant, and the derivative term neoplastic stem cell be adopted to identify the cells responsible for the long-term maintenance of such clones. Neoplastic clones would thus include those that never evolve further, as well as those that eventually give rise to fully malignant populations, and all stages in between. The term cancer stem cells would then be more appropriately restricted to cells generating subclones that have established malignant properties. More precise molecular understanding of the different stem cell states thus distinguished should contribute to the development of more effective prognostic and therapeutic tools for cancer diagnosis and treatment. Cancer Res; 73(3);

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Section: Normal Neoplastic and Cancer Scsmentioning

confidence: 99%

Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications

et al. 2013

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“…In contrast, SUFU-related Gorlin syndrome is highly associated with medulloblastoma predisposition, with three of nine Gorlin syndrome patients with germline SUFU mutations developing medulloblastoma in the same series (20). Germline nonsense mutations, missense mutations, and deletions in SUFU have been described in families with medulloblastoma (20,23).…”

Section: Genotype-phenotype Correlations Of Medulloblastoma Riskmentioning

confidence: 99%

“…In one recent series, germline SUFU mutations were identified in eight of 131 medulloblastoma patients (23). Young age (<3 years) and specific histologic subtypes (extensive nodularity and desmoplastic/nodular types) were each associated with a higher likelihood of germline SUFU mutations (23).…”

Section: Genotype-phenotype Correlations Of Medulloblastoma Riskmentioning

confidence: 99%

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Foulkes

Kamihara

Evans

et al. 2017

Clinical Cancer Research

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153

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Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU). SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in SUFU mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive “rhabdoid” term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, each of which encodes a chromatin remodeling family member. SMARCA4 mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. Clin Cancer Res; 23(12); e62–e67. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.

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“…Grouping the desmoplastic/nodular and MBEN as one group, SUFU germline mutations were found in 70% of the patients that were less than three years old at the time of diagnosis. Of more than 100 patients belonging to other histological subtypes, only one patient had SUFU germline mutations [70]. In the last five years, several studies have shown that these histological subtypes are clearly linked to different molecular signatures, raising the question of genetic screening of all patients with desmoplastic/nodular and MBEN [71][72][73], in particular, with patients younger than three years of age [70].…”

Section: Cns Tumorsmentioning

confidence: 99%

Recent developments in brain tumor predisposing syndromes

2015

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High Frequency of Germline SUFU Mutations in Children With Desmoplastic/Nodular Medulloblastoma Younger Than 3 Years of Age

Abstract: These data indicate that germline SUFU mutations were responsible for a high proportion of desmoplastic medulloblastoma in children younger than 3 years of age. Genetic testing should be offered to all children diagnosed with sonic hedgehog-driven medulloblastoma at a young age.

Cited by 107 publications

References 23 publications

Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications

Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Recent developments in brain tumor predisposing syndromes

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