| RRC ID |
45413
|
| 著者 |
Sadahira Y, Sugihara T, Fujiwara H, Nishimura H, Suetsugu Y, Takeshita M, Okamura S, Goto M.
|
| タイトル |
WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome.
|
| ジャーナル |
Virchows Arch
|
| Abstract |
Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.
|
| 巻・号 |
466(3)
|
| ページ |
343-50
|
| 公開日 |
2015-3-1
|
| DOI |
10.1007/s00428-014-1703-6
|
| PMID |
25503078
|
| MeSH |
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers / metabolism
Cell Line
Child
Child, Preschool
Erythroblasts / metabolism*
Erythroblasts / pathology
Exodeoxyribonucleases / genetics
Exodeoxyribonucleases / metabolism*
Female
Humans
Immunohistochemistry
Infant
Infant, Newborn
Male
Mass Screening
Middle Aged
Mutation / genetics
RecQ Helicases / genetics
RecQ Helicases / metabolism*
Werner Syndrome / diagnosis*
Werner Syndrome / metabolism*
Werner Syndrome / pathology
Werner Syndrome Helicase
Young Adult
|
| IF |
2.906
|
| 引用数 |
2
|
|
WOS 分野
|
PATHOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
K562
NB1RGB(RCB0222) |
