Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay

Citation
Tj. M'Soka et al., Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay, LEUKEMIA, 14(5), 2000, pp. 935-940
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA
ISSN journal
0887-6924 → ACNP
Volume
14
Issue
5
Year of publication
2000
Pages
935 - 940
Database
ISI
SICI code
0887-6924(200005)14:5<935:DOMP(A>2.0.ZU;2-8
Abstract
Methylthioadenosine phosphorylase (MTAP) deficiency in tumors can be therap eutically exploited for selective therapy. Many tumors lacking MTAP have be en found to homozygously delete the chromosome 9p region containing the p16 tumor suppressor gene. Several methods have been used to detect chromosome 9p deletions in primary tumors. However, the accurate diagnosis of chromos ome 9p deletions has been hampered by the presence of contaminating normal cells. In search of an accurate and sensitive diagnostic method, we have de veloped the real-time polymerase chain reaction assay using the TaqMan chem istry for quantitative detection of MTAP and p16 gene deletions. The assay' s feasibility was tested with peripheral blood leukocytes (PBL) from 29 pat ients with adult T cell leukemia (ATL) previously analyzed with Southern bl ot analysis and validated on 39 PBL or bone marrow samples from childhood T cell acute lymphoblastic leukemia (T-ALL). Homozygous deletions of MTAP an d pie genes were detected respectively in six (20.7%) and eight (27.6%) of 29 ATL samples and in 15 (38.5%) and 23 (59%) of 39 T-ALL samples. The resu lts correlated well with those of Southern blot analysis. It is of signific ance that the newly developed method can successfully detect homozygous del etions of these genes in samples containing as low as 33% blast cells. This rapid and sensitive method may be useful in searching for candidates for s elective therapy targeting MTAP deficiency.