title: Genome-Wide Single-Nucleotide Polymorphism Array Analysis Improves Prognostication of Acute Lymphoblastic Leukemia/Lymphoma.
abstract: Chromosomal abnormalities are important for the risk stratification of acute lymphoblastic leukemia/lymphoma (ALL). However, approximately 30% of pediatric and 50% of adult patients lack abnormalities with clinical relevance by traditional cytogenetic analysis. We integrated cytogenetic, fluorescence in situ hybridization, and whole-genome single-nucleotide polymorphism array results from 60 consecutive clinical ALL cases. By cytogenetic and/or fluorescence in situ hybridization analyses, recurring abnormalities with clinical relevance were observed in 33 B-cell ALL (B-ALL), including t(9;22), hyperdiploidy, KMT2A translocation, ETV6-RUNX1, intrachromosomal amplification of chromosome 21, near haploidy or low hypodiploidy, and t(8;22). Single-nucleotide polymorphism array analysis found additional aberrations with prognostic or therapeutic implication in 21 B-ALL and two T-cell ALL, including IKZF1 deletion, intrachromosomal amplification of chromosome 21 (one case with a normal karyotype), low hypodiploidy (two cases with a normal karyotype), and one case each with fusion genes ETV6-NTRK3, CRLF2-P2RY8, NUP214-ABL1, and SET-NUP214. IKZF1 deletion was noted in nine B-ALL with t(9;22), one B-ALL with t(4;11), five B-ALL with a normal karyotype, and three B-ALL with nonrecurring karyotypic abnormalities. Combining single-nucleotide polymorphism array with chromosome and fluorescence in situ hybridization assays, the detection rate for clinically significant abnormal results increased from 56% to 75%. Whole-genome single-nucleotide polymorphism array analysis detects cytogenetically undetectable clinically significant aberrations and should be routinely applied at diagnosis of ALL.
authors.affiliation: Clinical Cytogenetics Laboratory, University of Michigan, Ann Arbor, Michigan; Department of Pathology, Peking University First Hospital, Beijing, China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Cytogenetics Laboratory, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sue
authors.initials: S
authors.lastname: Miller
authors.affiliation: Clinical Cytogenetics Laboratory, University of Michigan, Ann Arbor, Michigan.
authors.forename: Diane
authors.initials: D
authors.lastname: Roulston
authors.affiliation: Department of Pathology, and the Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Dale
authors.initials: D
authors.lastname: Bixby
authors.affiliation: Clinical Cytogenetics Laboratory, University of Michigan, Ann Arbor, Michigan. Electronic address: linashao@med.umich.edu.
authors.forename: Lina
authors.initials: L
authors.lastname: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D055106:Genome-Wide Association Study; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion