TY - JOUR
T1 - Pediatric brain tumors
T2 - Mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage
AU - Cetica, Valentina
AU - Genitori, Lorenzo
AU - Giunti, Laura
AU - Sanzo, Massimiliano
AU - Bernini, Gabriella
AU - Massimino, Maura
AU - Sardi, Iacopo
PY - 2009
Y1 - 2009
N2 - Alkylating agents, commonly used for brain tumor therapy, induce DNA and RNA lesions that, if not repaired, drive cells to apoptosis. Thus, cellular mechanisms that are responsible for nucleic acid repair are possibly involved in drug resistance. This work analyzes hABH2 and hABH3, two human Fe(II)-dependent dioxygenases in pediatric brain tumors that are treated with alkylating agents. We analyzed 25 brain tumor samples for hABH2 and hABH3 mutations; a subset of samples was tested for quantitative expression with Real-Time PCR. Sequencing analysis showed two new mutations in two glioma patients, one of hABH2 coding sequence (I141 V) and the other of hABH3 (D189 N). The mutation at codon 189 falls in a crucial region of the protein. All subjects analyzed by Real-Time PCR showed an enhanced expression of the two genes, particularly of hABH2. This is the first study of hABH2 and hABH3 in pediatric brain tumors; further molecular investigations of their mutations and expression may help determine their role in response to chemotherapy.
AB - Alkylating agents, commonly used for brain tumor therapy, induce DNA and RNA lesions that, if not repaired, drive cells to apoptosis. Thus, cellular mechanisms that are responsible for nucleic acid repair are possibly involved in drug resistance. This work analyzes hABH2 and hABH3, two human Fe(II)-dependent dioxygenases in pediatric brain tumors that are treated with alkylating agents. We analyzed 25 brain tumor samples for hABH2 and hABH3 mutations; a subset of samples was tested for quantitative expression with Real-Time PCR. Sequencing analysis showed two new mutations in two glioma patients, one of hABH2 coding sequence (I141 V) and the other of hABH3 (D189 N). The mutation at codon 189 falls in a crucial region of the protein. All subjects analyzed by Real-Time PCR showed an enhanced expression of the two genes, particularly of hABH2. This is the first study of hABH2 and hABH3 in pediatric brain tumors; further molecular investigations of their mutations and expression may help determine their role in response to chemotherapy.
KW - Brain/central nervous system cancers
KW - DNA damage
KW - Drug resistance
KW - Pediatric cancers
KW - Repair mechanisms
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U2 - 10.1007/s11060-009-9837-0
DO - 10.1007/s11060-009-9837-0
M3 - Article
C2 - 19290481
AN - SCOPUS:68949136580
VL - 94
SP - 195
EP - 201
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -