Detection of homozygous deletions of the cyclin-dependent kinase 4 inhibitor (p16) gene in acute lymphoblastic leukemia and association with adverse prognostic features

Autor: M Fizzotti, F Lo Coco, Giuliana Alimena, C Quartarone, Franco Mandelli, Pier Giuseppe Pelicci, Simona Pisegna, Giuseppe Cimino
Rok vydání: 1995
Předmět:
Male
Biochemistry
law.invention
Exon
law
Adolescent
Adult
Base Sequence
Carrier Proteins
Child
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p16
DNA Primers
DNA
Neoplasm
Female
Humans
Immunophenotyping
Middle Aged
Molecular Sequence Data
Polymorphism
Single-Stranded Conformational
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Protein-Serine-Threonine Kinases
Sequence Deletion
Cyclin-Dependent Kinases
Genes
Tumor Suppressor
Proto-Oncogene Proteins
Polymerase chain reaction
biology
Single-Stranded Conformational
Hematology
Leukemia
Tumor Suppressor
Tumor suppressor gene
Immunology
Protein Serine-Threonine Kinases
Acute lymphocytic leukemia
medicine
Polymorphism
Southern blot
Cyclin-dependent kinase 4
Point mutation
DNA
Cell Biology
medicine.disease
Genes
Cancer research
biology.protein
Neoplasm
Settore MED/15 - Malattie del Sangue
Zdroj: Scopus-Elsevier
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v85.10.2685.bloodjournal85102685
Popis: A recently described putative tumor suppressor gene, the cyclin-dependent kinase 4 inhibitor (p16), has been shown to be altered by deletions and/or point mutations in various human cancers. To assess the incidence and clinico-biologic correlations of p16 homozygous deletion in hemopoietic tumors, we studied a panel of 244 DNA samples representative of distinct acute (99 cases) and chronic (57 cases) leukemia subtypes, myelodysplastic (22 cases) and myeloproliferative (15 cases) syndromes, and lymphomas (51 cases). A 361-bp probe complementary to the p16 exon 2 gene sequences was generated by polymerase chain reaction and used in Southern blot hybridization against these tumor DNAs. Homozygous deletions of p16 (p16-/-) were detected in 10 of 58 (17%) cases of acute lymphoblastic leukemia (ALL) of either B or T lineage and in no other tumors. Single-strand conformation polymorphism analysis of p16 exons 1 and 2 was also performed in 40 of the 58 ALL cases and in 16 lymphomas. In no cases were point mutations detected. The comparison of clinical features at presentation in p16-/- and in p16 germline ALL cases showed a greater leukemic cell mass (P = .001) and higher white blood cell counts (P = .01) in the former group. Two ALL cases in which diagnostic and relapse DNA samples were available showed p16-/- in both specimens. We conclude that homozygous p16 gene deletions characterize a subset of ALL with features of aggressive disease.
Databáze: OpenAIRE
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