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Article: Frequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphoma

TitleFrequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphoma
Authors
Issue Date2002
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal Of Pathology, 2002, v. 161 n. 6, p. 2123-2131 How to Cite?
AbstractNasal natural killer (NK)/T-cell lymphoma (NL) frequently co-expresses Fas (Apo-1/CD95) and Fas ligand (FasL), but the tumor cells seldom undergo apoptosis. To determine the reason for failure of apoptosis, we examined Fas mRNA expression in 23 NL cases by reverse transcriptase-polymerase chain reaction and sequenced the entire coding region of the Fas gene in 15 of these cases for which the full-length Fas cDNA could be amplified. The reverse transcriptase-polymerase chain reaction analysis revealed that all of the 23 cases expressed Fas mRNA and the sequencing results showed that in addition to the commonly expressed wild-type Fas mRNA and four alternative splice variants detected in 7 cases, mutant Fas transcripts were present in 9 of the 15 (60%) cases sequenced. With confirmation of some Fas mutations at the gene level, 12 deletions in nine cases and one insertion in one case were eventually identified. To rule out any potential polymerase chain reaction artifacts, the same protocol was used to examine 10 reactive tonsils as a control. No aberrant transcripts associated with deletions were detected in these tonsils except for three alternative splice variants. All of the deletion variants detected in NL contained N-terminal preligand assembly domain but not C-terminal death domain and/or transmembrane domain. Codetection of the wild-type allele and the mutated Fas alleles without the death domain suggested that a dominant-negative mechanism could block the apoptosis signaling. Moreover, loss of the transmembrane domain could protect the tumor cells from apoptosis by producing a soluble form of the Fas receptor. The actuarial 3-year survivals leveled off at 15% for patients carrying the Fas mutations and/or splice variants in the lesions and 49% for those carrying the wild type only, but the difference did not reach statistical significance on the univariate analysis (P = 0.396). Taken together, the findings in this study suggest that frequent Fas gene mutations in NL can result in resistance to apoptosis and may contribute to the pathogenesis of NL by adding to the tumor immune privilege.
Persistent Identifierhttp://hdl.handle.net/10722/49123
ISSN
2015 Impact Factor: 4.206
2015 SCImago Journal Rankings: 2.653
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorShen, Len_HK
dc.contributor.authorLiang, ACTen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorAu, WYen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorLiang, RHSen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.date.accessioned2008-06-12T06:34:55Z-
dc.date.available2008-06-12T06:34:55Z-
dc.date.issued2002en_HK
dc.identifier.citationAmerican Journal Of Pathology, 2002, v. 161 n. 6, p. 2123-2131en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49123-
dc.description.abstractNasal natural killer (NK)/T-cell lymphoma (NL) frequently co-expresses Fas (Apo-1/CD95) and Fas ligand (FasL), but the tumor cells seldom undergo apoptosis. To determine the reason for failure of apoptosis, we examined Fas mRNA expression in 23 NL cases by reverse transcriptase-polymerase chain reaction and sequenced the entire coding region of the Fas gene in 15 of these cases for which the full-length Fas cDNA could be amplified. The reverse transcriptase-polymerase chain reaction analysis revealed that all of the 23 cases expressed Fas mRNA and the sequencing results showed that in addition to the commonly expressed wild-type Fas mRNA and four alternative splice variants detected in 7 cases, mutant Fas transcripts were present in 9 of the 15 (60%) cases sequenced. With confirmation of some Fas mutations at the gene level, 12 deletions in nine cases and one insertion in one case were eventually identified. To rule out any potential polymerase chain reaction artifacts, the same protocol was used to examine 10 reactive tonsils as a control. No aberrant transcripts associated with deletions were detected in these tonsils except for three alternative splice variants. All of the deletion variants detected in NL contained N-terminal preligand assembly domain but not C-terminal death domain and/or transmembrane domain. Codetection of the wild-type allele and the mutated Fas alleles without the death domain suggested that a dominant-negative mechanism could block the apoptosis signaling. Moreover, loss of the transmembrane domain could protect the tumor cells from apoptosis by producing a soluble form of the Fas receptor. The actuarial 3-year survivals leveled off at 15% for patients carrying the Fas mutations and/or splice variants in the lesions and 49% for those carrying the wild type only, but the difference did not reach statistical significance on the univariate analysis (P = 0.396). Taken together, the findings in this study suggest that frequent Fas gene mutations in NL can result in resistance to apoptosis and may contribute to the pathogenesis of NL by adding to the tumor immune privilege.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.relation.ispartofAmerican Journal of Pathologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAntigens, CD95 - genetics - metabolismen_HK
dc.subject.meshApoptosis - physiologyen_HK
dc.subject.meshKiller Cells, Natural - metabolismen_HK
dc.subject.meshLymphoma, T-Cell - genetics - pathologyen_HK
dc.subject.meshNose Neoplasms - genetics - pathologyen_HK
dc.titleFrequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9440&volume=161&issue=6&spage=2123&epage=2131&date=2002&atitle=Frequent+deletion+of+Fas+gene+sequences+encoding+death+and+transmembrane+domains+in+nasal+natural+killer/T-cell+lymphomaen_HK
dc.identifier.emailLu, L:liweilu@hkucc.hku.hken_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.emailLiang, RHS:rliang@hku.hken_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityLiang, RHS=rp00345en_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid12466128-
dc.identifier.pmcidPMC1850920en_HK
dc.identifier.scopuseid_2-s2.0-0036898013en_HK
dc.identifier.hkuros78439-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036898013&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume161en_HK
dc.identifier.issue6en_HK
dc.identifier.spage2123en_HK
dc.identifier.epage2131en_HK
dc.identifier.isiWOS:000179663400019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridShen, L=7401704659en_HK
dc.identifier.scopusauthoridLiang, ACT=14825292900en_HK
dc.identifier.scopusauthoridLu, L=7403963552en_HK
dc.identifier.scopusauthoridAu, WY=7202383089en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridLiang, RHS=26643224900en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK

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