Novel Mutations of Neurofibromatosis Type 1 Gene in Small Cell Lung Cancers

Furukawa, Ken‐Ichi; Yanai, Noboru; Fujita, Masatoshi; Harada, Yukio

doi:10.1007/s005950300074

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…Why, for example, are NF1 patients not predisposed to lung tumours given that at least 10% of all sporadic lung cancers have NF1 mutations [8, 65, 72, 166]?…”

Section: Main Bodymentioning

confidence: 99%

The NF1 somatic mutational landscape in sporadic human cancers

et al. 2017

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BackgroundNeurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia. However, acquired somatic mutations in NF1 are also found in a wide variety of malignant neoplasms that are not associated with NF1.Main bodyCapitalizing upon the availability of next-generation sequencing data from cancer genomes and exomes, we review current knowledge of somatic NF1 mutations in a wide variety of tumours occurring at a number of different sites: breast, colorectum, urothelium, lung, ovary, skin, brain and neuroendocrine tissues, as well as leukaemias, in an attempt to understand their broader role and significance, and with a view ultimately to exploiting this in a diagnostic and therapeutic context.ConclusionAs neurofibromin activity is a key to regulating the RAS/MAPK pathway, NF1 mutations are important in the acquisition of drug resistance, to BRAF, EGFR inhibitors, tamoxifen and retinoic acid in melanoma, lung and breast cancers and neuroblastoma. Other curiosities are observed, such as a high rate of somatic NF1 mutation in cutaneous melanoma, lung cancer, ovarian carcinoma and glioblastoma which are not usually associated with neurofibromatosis type 1. Somatic NF1 mutations may be critical drivers in multiple cancers. The mutational landscape of somatic NF1 mutations should provide novel insights into our understanding of the pathophysiology of cancer. The identification of high frequency of somatic NF1 mutations in sporadic tumours indicates that neurofibromin is likely to play a critical role in development, far beyond that evident in the tumour predisposition syndrome NF1.

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“…Why, for example, are NF1 patients not predisposed to lung tumours given that at least 10% of all sporadic lung cancers have NF1 mutations [8, 65, 72, 166]?…”

Section: Main Bodymentioning

confidence: 99%

The NF1 somatic mutational landscape in sporadic human cancers

et al. 2017

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“…NF1 plays the role of a tumor suppressor protein by inhibiting RAS. Mutations in NF1 have been reported in both NSCLC and small cell lung cancer [61,118,119]. It is possible that NF1 plays an important role in the pathogenesis of SQCC given that it is required for the normal development of epidermal cells.…”

Section: Nf1mentioning

confidence: 99%

Genomics of Squamous Cell Lung Cancer

2013

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“…In a separate study, Furukawa et al analyzed 37 patients with primary lung cancer and identified NF1 mutations in three patients, all of which had small cell lung carcinoma. All three mutations identified were located in the GTPase-activating protein (GAP)-related domain (GRD) close to the mutational hot spot within exon 24 [231]. Li et al have reported three cases of adenocarcinoma of the colon, myelodysplastic syndrome, and anaplastic astrocytoma, which also had NF1 mutations involving the GRD domain [232].…”

Section: Somatic Nf1 Mutationsmentioning

confidence: 99%

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations

2012

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After completing this course, the reader will be able to:1. Describe phenotypic and clinical features associated with neurofibromatosis 1. Identify malignant tumors associated with neurofibromatosis 1.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTIntroduction. Neurofibromatosis 1 is a tumor predisposition genetic syndrome with autosomal dominant inheritance and virtually 100% penetrance by the age of 5 years. NF1 results from a loss-of-function mutation in the NF1 gene, resulting in decreased levels of neurofibromin in the cell. Neurofibromin is a negative regulator of various intracellular signaling pathways involved in the cellular proliferation. Although the loss of heterozygosity in the NF1 gene may predispose NF1 patients to certain malignancies, additional genetic alterations are a prerequisite for their development. The precise nature of these additional genetic alterations is not well defined, and genetic testing of all malignancies in NF1 patients becomes an essential component of future research in this subset of patients. In addition to germline NF1 mutations, alteration of the somatic NF1 gene is associated

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Novel Mutations of Neurofibromatosis Type 1 Gene in Small Cell Lung Cancers

Abstract: A mutation in this region could imply a poor prognosis.

Cited by 12 publications

References 18 publications

The NF1 somatic mutational landscape in sporadic human cancers

The NF1 somatic mutational landscape in sporadic human cancers

Genomics of Squamous Cell Lung Cancer

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations

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