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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 病理學科所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57326
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dc.contributor.advisor鄭永銘(Yung-Ming Jeng)
dc.contributor.authorTsung-Lin Liuen
dc.contributor.author劉宗霖zh_TW
dc.date.accessioned2021-06-16T06:41:47Z-
dc.date.available2019-10-09
dc.date.copyright2014-10-09
dc.date.issued2014
dc.date.submitted2014-07-29
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57326-
dc.description.abstract從基因分型角度來看,肉瘤可被分為兩大類:一類是簡單染色體組型肉瘤;另一類是複雜色體組型肉瘤。
端粒的縮短為細胞分裂時必然發生的現象,當端粒縮短至一定程度後,細胞即停止分裂或死亡,腫瘤細胞要無限制地生長必須克服此一限制。目前已知克服端粒縮短的機制主要有兩種:一是活化端粒酶;另一則是透過端粒替代性延長(alternative lengthening of telomere, ALT)。在胰臟神經內分泌瘤(pancreatic neuroendocrine tumor, p-NET)中,此端粒替代性延長機制是由ATRX或DAXX失去表現所導致。
我們共收集了195例的肉瘤檢體,其中簡單染色體組型肉瘤共62例,及複雜染色體組型肉瘤133例。透過ATRX、DAXX免疫組織染色及端粒特異性螢光原位雜交,我們發現在複雜染色體組型的軟組織肉瘤中,常帶有ATRX表現量喪失(P = 0.049)及端粒替代性延長(P = 0.004)的現象。所有195例肉瘤中,DAXX並無表現喪失。在58例多形性未分化肉瘤中,共21例為經放射線治療後續發之惡性肉瘤。ATRX表現量喪失(P = 0.007)及端粒替代性延長(P < 0.001)常表現在多形性未分化肉瘤,但經放射線治療後續發之惡性肉瘤並無此現象發生。我們的研究結果顯示,在複雜染色體組型的軟組織肉瘤中,帶有ATRX表現量喪失的腫瘤常伴有表現端粒替代性延長機制,且在多形性未分化肉瘤當中,ATRX表現量喪失及端粒替代性延長是其維持端粒長度的主要機制。
zh_TW
dc.description.abstractFrom a genetic perspective, sarcomas tend to fall into two groups: one is sarcomas with simple karyotypes and other one is sarcomas with complex karyotypes.
Telomere shortening is an inevitable phenomenon during cell division. Once telomere has shortened to a critical length, cells undergo replicative senescence. Tumor cells must overcome this limitation to become immortal. There are two major mechanisms for telomere length maintenance; one is the activation of telomerase. The other is the alternative lengthening of telomeres, which in pancreatic neuroendocrine tumor is caused by mutation and loss of expression of either ATRX or DAXX.
We collected 195 cases of sarcoma which were composed of 62 type I sarcomas and 133 type II sarcomas. By immunohistochemical stain of ATRX/DAXX and telomere-specific fluorescence in situ hybridization, we found ATRX was frequently loss (P = 0.049) and ALT usually occurred in karyotype-complex sarcomas (P = 0.004). None of the 195 cases lost DAXX expression. Within the 58 cases of undifferentiated pleomorphic sarcoma, 21 cases were post-irradiation sarcoma. Both ATRX loss of expression (P = 0.007) and ALT (P < 0.001) occur in undifferentiated pleomorphic sarcoma but not in post-irradiation sarcoma. Our results indicate that loss of ATRX is associated with ALT phenotype in karyotype-complex sarcoma and ATRX loss and ALT is a major mechanism of telomere preservation in undifferentiated pleomorphic sarcoma.
en
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en
dc.description.tableofcontents口試委員審定書 II
謝辭 III
中文摘要 IV
Abstract V
Contents VII
1.Introduction 1
1.1 Soft tissue sarcoma 1
1.2 Telomere and telomerase 3
1.3 Telomere maintenance 4
1.4 Activation of telomerase 4
1.5 Alternative lengthening of telomere (ALT) 5
1.6 Alpha thalassemia/mental retardation syndrome X-linked (ATRX) 7
1.7 Death domain-associated protein (DAXX) 7
1.8 Aims of this study 9
2. Materials and Methods 10
2.1 Immunohistochemical stain 10
2.2 Fluorescence in situ hybridization 11
2.3 Statistical analysis 12
3.Results 13
3.1 Study cohort 13
3.2 ATRX is frequently loss in some types of sarcoma but DAXX is not 13
3.3 ATRX is frequently loss in undifferentiated pleomorphic sarcoma 14
3.4 Frequent ALT in type II sarcomas 14
3.5 Frequent ALT in undifferentiated pleomorphic sarcoma 14
3.6 Association of ALT and ATRX loss in undifferentiated pleomorphic sarcomas 15
4.Discussion 16
5. Figures and Tables 20
Table 1. The expression of ATRX and DAXX in various sarcomas 20
Table 2. ATRX expression in undifferentiated pleomorphic sarcoma 21
Table 3. Alternative lengthening of telomeres phenotype in different type of sarcoma 22
Figure 1. H&E, DAXX and ATRX immunohistochemical stain in alveolar rhabdomyosarcoma 23
Figure 2. H&E, DAXX and ATRX immunohistochemical stain in dermatofibrosarcoma protuberans (DFSP) 24
Figure 3. DAXX and ATRX immunohistochemical stain in gastrointestinal stromal tumor (GIST) 25
Figure 4. H&E, DAXX and ATRX immunohistochemical stain in primitive neuroectodermal tumor (PNET) 26
Figure 5. H&E, DAXX and ATRX immunohistochemical stain in synovial sarcoma 27
Figure 6. H&E, DAXX and ATRX immunohistochemical stain in botryoid rhabdomyosarcoma 28
Figure 7. H&E, DAXX and ATRX immunohistochemical stain in chondrosarcoma 29
Figure 8. H&E, DAXX and ATRX immunohistochemical stain, and telomere-specific FISH in embryonal rhabdomyosarcoma 30
Figure 9. H&E, DAXX and ATRX immunohistochemical stain in malignant solitary fibrous tumor 32
Figure 10. DAXX and ATRX immunohistochemical stain in malignant peripheral nerve sheath tumor (MPNST) 33
Figure 11. H&E, DAXX and ATRX immunohistochemical stain, and telomere-specific FISH in myxofibrosarcoma 34
Figure 12. H&E, DAXX and ATRX immunohistochemical stain in osteosarcoma 36
Figure 13. H&E, DAXX and ATRX immunohistochemical stain in pleomorphic rhabdomyosarcoma 37
Figure 14. H&E, DAXX and ATRX immunohistochemical stain, and telomere-specific FISH in undifferentiated pleomorphic sarcoma 38
Table 6. Alternative lengthening of telomere phenotype in sarcomas 41
6.Reference 42
dc.language.isoen
dc.subject端粒維持zh_TW
dc.subject端粒替代性延長zh_TW
dc.subject軟組織肉瘤zh_TW
dc.subjectATRXzh_TW
dc.subjectalternative lengthening of telomeres (ALT)en
dc.subjecttelomere maintenanceen
dc.subjectATRXen
dc.subjectsoft tissue sarcomaen
dc.title軟組織肉瘤ATRX表現喪失及端粒替代性延長和腫瘤分類的關係zh_TW
dc.titleLoss of ATRX expression and alternative lengthening of telomere in soft tissue sarcoma: the relationship with tumor classificationen
dc.typeThesis
dc.date.schoolyear102-2
dc.description.degree碩士
dc.contributor.oralexamcommittee陳彥榮(Yen-Rong Chen),周涵怡(Han-Yi Chou),連晃駿(Huang-Chun Lien)
dc.subject.keyword端粒維持,端粒替代性延長,ATRX,軟組織肉瘤,zh_TW
dc.subject.keywordtelomere maintenance,alternative lengthening of telomeres (ALT),ATRX,soft tissue sarcoma,en
dc.relation.page48
dc.rights.note有償授權
dc.date.accepted2014-07-29
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept病理學研究所zh_TW
Appears in Collections:病理學科所

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