Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia. Issue 4 (5th March 2013)

• Record Type: Journal Article
• Authors: Boudry‐Labis, Elise; Roche‐Lestienne, Catherine; Nibourel, Olivier; Boissel, Nicolas; Terre, Christine; Perot, Christine; Eclache, Virginie; Gachard, Nathalie; Tigaud, Isabelle; Plessis, Ghislaine; Cuccuini, Wendy; Geffroy, Sandrine; Villenet, Céline; Figeac, Martin; Leprêtre, Frederic; Renneville, Aline; Cheok, Meyling; Soulier, Jean; Dombret, Hervé; Preudhomme, Claude
• Is Part Of: American journal of hematology. Volume 88:Issue 4(2013:Apr.)
• Page Start: 306
• Page End: 311
• Publication Date: 2013-03-05
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23403
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Germline heterozygous alterations of the tumor‐suppressor gene <italic>neurofibromatosis‐1</italic> (<italic>NF1</italic>) lead to neurofibromatosis type 1, a genetic disorder characterized by a higher risk to develop juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML). More recently, somatic 17q11 deletions encompassing <italic>NF1</italic> have been described in many adult myeloid malignancies. In this context, we aimed to define <italic>NF1</italic> involvement in AML. We screened a total of 488 previously untreated de novo AML patients for the <italic>NF1</italic> deletion using either array comparative genomic hybridization (aCGH) or real‐time quantitative PCR/fluorescence in situ hybridization approaches. We also applied massively parallel sequencing for in depth mutation analysis of <italic>NF1</italic> in 20 patients including five <italic>NF1</italic>‐deleted patients. We defined a small ∼0.3 Mb minimal deleted region involving <italic>NF1</italic> by aCGH and an overall frequency of <italic>NF1</italic> deletion of 3.5% (17/485). <italic>NF1</italic> deletion is significantly associated with unfavorable cytogenetics and with monosomal karyotype notably. We discovered six <italic>NF1</italic> variants of unknown significance in 7/20 patients of which only one out of four disappeared in corresponding complete remission sample. In addition, only one out of five <italic>NF1</italic>‐deleted patients has an acquired coding mutation in the remaining allele. In conclusion, direct <italic>NF1</italic> inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression. Am. J. Hematol. 88:306–311, 2013. © 2013 Wiley Periodicals, Inc.</p> </abstract>