Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome

Ohtake, Akira; Aoki, Yoko; Saito, Yuka; Niihori, Tetsuya; Shibuya, Akira; Kure, Shigeo; Matsubara, Yoichi

doi:10.1097/mph.0b013e3181df5e5b

Cited by 15 publications

(12 citation statements)

References 32 publications

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“…Both had BRAF mutations that have been reported in other individuals with CFC syndrome without accompanying malignancy. Non‐Hodgkins lymphoma was reported in one [Ohtake et al, 2010]. One boy with a BRAF mutation and a parasagittal meningioma is known to the support group CFC International.…”

Section: Discussionmentioning

confidence: 99%

Cardio‐facio‐cutaneous syndrome: Does genotype predict phenotype?

Allanson

Annerén

Aoki

et al. 2011

American J of Med Genetics Pt C

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Cardio-facio-cutaneous syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10–30% of individuals with a clinical diagnosis of cardio-facio-cutaneous, a mutation in one of these causative genes is not found. Cardinal features of cardio-facio-cutaneous include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype-phenotype correlations. This clinical study of 186 children and young adults with mutation-proven cardio-facio-cutaneous syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (~75%), while 46 (~25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al., 1986]. While some clinical data on 136 are in the literature, fifty are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype-phenotype correlation, being more common in individuals with a BRAF mutation.

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Section: Discussionmentioning

confidence: 99%

Cardio‐facio‐cutaneous syndrome: Does genotype predict phenotype?

Allanson

Annerén

Aoki

et al. 2011

American J of Med Genetics Pt C

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“…The numbers of patients affected by these disorders are too low for a thorough statistical analysis, and descriptions of patients developing a malignant disorder are limited to case reports. [341][342][343][344][345] However, close monitoring of patients with all germline Ras/MAPK disorders, including LEOPARD and CFC syndromes, for the occurrence of neoplasias is often suggested.…”

Section: Raf Mutations In Developmental Syndromesmentioning

confidence: 99%

Raf Family Kinases: Old Dogs Have Learned New Tricks

et al. 2011

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First identified in the early 1980s as retroviral oncogenes, the Raf proteins have been the objects of intense research. The discoveries 10 years later that the Raf family members (Raf-1, B-Raf, and A-Raf) are bona fide Ras effectors and upstream activators of the ubiquitous ERK pathway increased the interest in these proteins primarily because of the central role that this cascade plays in cancer development. The important role of Raf in cancer was corroborated in 2002 with the discovery of B-Raf genetic mutations in a large number of tumors. This led to intensified drug development efforts to target Raf signaling in cancer. This work yielded not only recent clinical successes but also surprising insights into the regulation of Raf proteins by homodimerization and heterodimerization. Surprising insights also came from the hunt for new Raf targets. Although MEK remains the only widely accepted Raf substrate, new kinase-independent roles for Raf proteins have emerged. These include the regulation of apoptosis by suppressing the activity of the proapoptotic kinases, ASK1 and MST2, and the regulation of cell motility and differentiation by controlling the activity of Rok-α. In this review, we discuss the regulation of Raf proteins and their role in cancer, with special focus on the interacting proteins that modulate Raf signaling. We also describe the new pathways controlled by Raf proteins and summarize the successes and failures in the development of efficient anticancer therapies targeting Raf. Finally, we also argue for the necessity of more systemic approaches to obtain a better understanding of how the Ras-Raf signaling network generates biological specificity.

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“…In ∼200 individuals with CFC reported in the literature, 3 have been found to have acute lymphoblastic leukemia, 10,14,72 one with non-Hodgkin lymphoma, 73 and one with large B-cell lymphoma. One individual with CFC (BRAF mutation) had a hepatoblastoma, possibly the result of postcardiac transplant immunosuppression.…”

Section: Hematology/oncology Conditionsmentioning

confidence: 99%

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

et al. 2014

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Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

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Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome

Cited by 15 publications

References 32 publications

Cardio‐facio‐cutaneous syndrome: Does genotype predict phenotype?

Cardio‐facio‐cutaneous syndrome: Does genotype predict phenotype?

Raf Family Kinases: Old Dogs Have Learned New Tricks

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

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