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No evidence for mutations or altered expression of the Suppressor of Fused gene (SUFU) in primitive neuroectodermal tumours
Author(s) -
Koch A.,
Waha A.,
Hartmann W.,
Milde U.,
Goodyer C. G.,
Sörensen N.,
Berthold F.,
DigonSöntgerath B.,
Krätzschmar J.,
Wiestler O. D.,
Pietsch T.
Publication year - 2004
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2004.00560.x
Subject(s) - biology , wnt signaling pathway , sonic hedgehog , genetics , loss of heterozygosity , hedgehog , hedgehog signaling pathway , cancer research , adenomatous polyposis coli , tumor suppressor gene , germline mutation , gene , mutation , exon , microbiology and biotechnology , allele , cancer , carcinogenesis , colorectal cancer
The sonic hedgehog (Shh) and the Wnt signalling pathways are involved in the development of medulloblastomas (MBs), the most frequent malignant brain tumours in children. Components of these two developmental and cancer‐associated pathways, including ( Patched ) PTCH , SMOH , adenomatous polyposis coli ( APC ) , β‐catenin and AXIN1 show somatic mutations in sporadic MBs. In this study we analysed SUFU ( human suppressor of fused ), which acts as a negative regulator of both the Shh and Wnt signalling pathways and therefore represents a putative tumour suppressor gene, to find out if it is also involved in the pathogenesis of sporadic MBs. We screened 145 primitive neuroectodermal tumours (PNETs) including 90 classic MBs, 42 of the desmoplastic variant and two medullomyoblastomas as well as 11 M B cell lines for mutations using single‐strand conformational polymorphism (SSCP) and sequencing analysis. 18% of the MBs exhibited allelic losses on chromosome 10q. In contrast to a previous report, in which truncating mutations of SUFU have been identified in 9% of MBs, we were not able to identify somatic mutations of SUFU in our large tumour panel. We uncovered single nucleotide polymorphisms (SNPs) in exon 4, 8, 11 and in intron 2 in the SUFU gene. Expression analysis by competitive reverse transciption‐polymerase chain reaction (RT‐PCR) revealed no difference in SUFU mRNA levels of both MB subtypes and normal foetal or adult cerebellar tissues. Our results indicate that genetic alterations of the SUFU gene, do not contribute significantly to the molecular pathogenesis of MBs.