Type 2A gene research - from Japan

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Abstract from Int J Oncol. 2003 Sep;23(3):737-44.

Genomic structure and mutational analysis of the human KIF1Balpha gene

located at 1p36.2 in neuroblastoma.

Chen YY, Takita J, Chen YZ, Yang HW, Hanada R, Yamamoto K, Hayashi Y.

Department of Pediatrics, Graduate School of Medicine, University of

Tokyo, Tokyo 113-8655, Japan.

KIF1a is a member of the kinesin superfamily proteins that are

microtubule-dependent molecular motors involved in important

intracellular functions such as organelle transport and cell division.

We previously determined the structure of the human KIF1Bbeta gene,

which was found to be a homologue of the murine Kif1bbeta, and

demonstrated that the human KIF1Bbeta is a causative gene of

Charcot-Marie-Tooth

disease type 2A although we did not prove that it is a tumor suppressor

gene of neuroblastoma. Here, we identified another isoform of the human

KIF1B gene, KIF1Balpha. The KIF1Balpha and KIF1Bbeta are alternative

splicing products of the KIF1B gene located on 1p36.2. The KIF1Balpha is

distinct from KIF1Bbeta in the C-terminal cargo-binding domain; however,

they have the same N-terminal motor domain. We found that the transcript

of approximately 7.8 kb of KIF1Balpha was expressed in several tissues,

especially in skeletal muscle, by Northern blot analysis. To determine

whether this gene is one of the candidate tumor suppressor genes for

neuroblastoma (NB) or other pediatric solid tumors, we performed

mutational screening of KIF1Balpha in 25 NB, 9 rhabdomyosarcoma, 12

Ewing sarcoma and 24 other pediatric solid tumor cell lines. Using

RT-PCR single-strand conformation polymorphism analysis and direct

sequencing we detected a missense mutation (M807I) in 1 NB cell line

(SK-N-SH), 3 silent mutations in 2 NB cell lines and 1 primitive

neuroectodermal tumor cell line, respectively. RT-PCR analysis revealed

that KIF1Balpha was obviously

expressed in almost all of the tumor cell lines examined except NB-1.

Furthermore, real-time quantitative RT-PCR showed that there was no

significant difference in KIF1Balpha expression between 14 early-stage

(stage I and II) and 14 advanced-stage (stage III and IV) NB fresh tumor

specimens. These results suggest that KIF1Ba in addition to KIF1Bbeta

may not be a candidate tumor suppressor gene for NB.