title: Interleukin-7 receptor-α gene mutations are not detected in adult T-cell acute lymphoblastic leukemia.
abstract: Somatic mutations in cancer cell genes are classified according to their functional significance. Those that provide the malignant cells with significant advantage are collectively referred to as driver mutations and those that do not, are the passenger mutations. Accordingly, analytical criteria to distinguish driver mutations from passenger mutations have been recently suggested. Recent studies revealed mutations in interleukin-7 receptor-α (IL7R) gene in 10% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients and in only a few cases of pediatric B-ALL. IL7R mutations are also frequently found in patients with lung cancer, but whereas in pediatric T-ALL IL7R mutations are "drivers" (consisting of gain-of-function mutations within a narrow 50-base pair interval at exon 6 that confer cytokine-independent cell growth and promote tumor transformation), in lung cancer, mutations are substitution mutations randomly distributed across the gene and are probably only "passenger" events. Because the treatment response of adult T-ALL is significantly poorer than that of childhood T-ALL and because exon 6 IL7R mutations play a role in the pathogenesis of childhood T-ALL, we sought to determine how the pattern of IL7R mutations varies between adult and childhood T-ALL. To that end, we sequenced the 50-base pair interval in exon 6 of the IL7R of DNA obtained from bone marrow samples of 35 randomly selected adult patients with T-ALL. Our analysis revealed that none of these 35 samples carried an IL7R mutation in exon 6. Whether differences in the genetic makeup of adult and childhood T-ALL explain the differential response to therapy remains to be determined.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovski
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Maro
authors.initials: M
authors.lastname: Ohanian
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D054316:Biomarkers, Pharmacological; D002648:Child; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D054316:Biomarkers, Pharmacological; D053699:Interleukin-7 Receptor alpha Subunit
keywords: Cancer genetics; IL7rR mutations; T-ALL; hematalogical cancer