Mutation analysis of the p73 gene in nonastrocytic brain tumours.
Loss of heterozygosity (LOH) involving the distal chromosome 1 p36 region occurs frequently in nonastrocytic brain tumours, but the tumour suppressor gene targeted by this deletion is unknown. p73 is a novel gene that has high sequence homology and similar gene structure to the p53 gene; it has been mapped to 1 p36, and may thus represent a candidate for this tumour suppressor gene. To determine whether p73 is involved in nonastrocytic brain tumour development, we analysed 65 tumour samples including 26 oligodendrogliomas, 4 ependymomas, 5 medulloblastomas, 10 meningiomas, 2 meningeal haemangiopericytomas, 2 neurofibrosarcomas, 3 primary lymphomas, 8 schwannomas and 5 metastatic tumours to the brain, for p73 alterations. Characterization of allelic loss at 1 p36-p35 showed LOH in about 50% of cases, primarily involving oligodendroglial tumours (22 of 26 cases analysed; 85%) and meningiomas (4 of 10; 40%). PCR-SSCP and direct DNA sequencing of exons 2 to 14 of p73 revealed a missense mutation in one primary lymphoma: a G-to-A transition, with Glu291Lys change. 8 additional cases displayed no tumour-specific alterations, as 3 distinct polymorphic changes were identified: a double polymorphic change of exon 5 was found in one ependymoma and both samples derived from an oligodendroglioma, as follows: a G-to-A transition with no change in Pro 146, and a C-to-T variation with no change in Asn 204: a delG at exon 3/+12 position was identified in 4 samples corresponding to 2 oligodendrogliomas, 1 ependymoma and 1 meningioma, and a C-to-T change at exon 2/+10 position was present in a metastatic tumour. Although both LOH at 1 p36 and p73 sequence changes were evidenced in 4 cases, it is difficult to establish a causal role of the p73 variations and nonastrocytic brain tumours development.
Alonso
M E
ME
Laboratorio de Oncogenética Molecular, Departamento de Cirugia Experimental, Unidad de Investigación, Hospital Universitario La Paz, Madrid, 28046, Spain.
Bello
M J
MJ
Gonzalez-Gomez
P
P
Lomas
J
J
Arjona
D
D
de Campos
J M
JM
Kusak
M E
ME
Sarasa
J L
JL
Isla
A
A
Rey
J A
JA
D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins