Conţinutul numărului revistei |
Articolul precedent |
Articolul urmator |
383 0 |
SM ISO690:2012 KAMAL, Maud, LAMEIRAS, Sonia, SAMEŢ, Nina, NOI, Autori. Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site. In: British Journal of Cancer, 2021, nr. 4(124), pp. 777-785. ISSN 0007-0920. DOI: https://doi.org/10.1038/s41416-020-01153-4 |
EXPORT metadate: Google Scholar Crossref CERIF DataCite Dublin Core |
British Journal of Cancer | ||||||
Numărul 4(124) / 2021 / ISSN 0007-0920 /ISSNe 1532-1827 | ||||||
|
||||||
DOI:https://doi.org/10.1038/s41416-020-01153-4 | ||||||
Pag. 777-785 | ||||||
|
||||||
Rezumat | ||||||
Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability. |
||||||
Cuvinte-cheie Human papilloma virus 16, Oropharyngeal Neoplasms, Viral Genes |
||||||
|
Cerif XML Export
<?xml version='1.0' encoding='utf-8'?> <CERIF xmlns='urn:xmlns:org:eurocris:cerif-1.5-1' xsi:schemaLocation='urn:xmlns:org:eurocris:cerif-1.5-1 http://www.eurocris.org/Uploads/Web%20pages/CERIF-1.5/CERIF_1.5_1.xsd' xmlns:xsi='http://www.w3.org/2001/XMLSchema-instance' release='1.5' date='2012-10-07' sourceDatabase='Output Profile'> <cfResPubl> <cfResPublId>ibn-ResPubl-126218</cfResPublId> <cfResPublDate>2021-02-16</cfResPublDate> <cfVol>124</cfVol> <cfIssue>4</cfIssue> <cfStartPage>777</cfStartPage> <cfISSN>0007-0920</cfISSN> <cfURI>https://ibn.idsi.md/ro/vizualizare_articol/126218</cfURI> <cfTitle cfLangCode='EN' cfTrans='o'>Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site</cfTitle> <cfKeyw cfLangCode='EN' cfTrans='o'>Human papilloma virus 16; Oropharyngeal Neoplasms; Viral Genes</cfKeyw> <cfAbstr cfLangCode='EN' cfTrans='o'><p>Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability. </p></cfAbstr> <cfResPubl_Class> <cfClassId>eda2d9e9-34c5-11e1-b86c-0800200c9a66</cfClassId> <cfClassSchemeId>759af938-34ae-11e1-b86c-0800200c9a66</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfResPubl_Class> <cfResPubl_Class> <cfClassId>e601872f-4b7e-4d88-929f-7df027b226c9</cfClassId> <cfClassSchemeId>40e90e2f-446d-460a-98e5-5dce57550c48</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfResPubl_Class> <cfPers_ResPubl> <cfPersId>ibn-person-87220</cfPersId> <cfClassId>49815870-1cfe-11e1-8bc2-0800200c9a66</cfClassId> <cfClassSchemeId>b7135ad0-1d00-11e1-8bc2-0800200c9a66</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfPers_ResPubl> <cfPers_ResPubl> <cfPersId>ibn-person-87221</cfPersId> <cfClassId>49815870-1cfe-11e1-8bc2-0800200c9a66</cfClassId> <cfClassSchemeId>b7135ad0-1d00-11e1-8bc2-0800200c9a66</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfPers_ResPubl> <cfPers_ResPubl> <cfPersId>ibn-person-32816</cfPersId> <cfClassId>49815870-1cfe-11e1-8bc2-0800200c9a66</cfClassId> <cfClassSchemeId>b7135ad0-1d00-11e1-8bc2-0800200c9a66</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfPers_ResPubl> <cfPers_ResPubl> <cfPersId>ibn-person-93022</cfPersId> <cfClassId>49815870-1cfe-11e1-8bc2-0800200c9a66</cfClassId> <cfClassSchemeId>b7135ad0-1d00-11e1-8bc2-0800200c9a66</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> </cfPers_ResPubl> <cfFedId> <cfFedIdId>ibn-doi-126218</cfFedIdId> <cfFedId>10.1038/s41416-020-01153-4</cfFedId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> <cfFedId_Class> <cfClassId>31d222b4-11e0-434b-b5ae-088119c51189</cfClassId> <cfClassSchemeId>bccb3266-689d-4740-a039-c96594b4d916</cfClassSchemeId> </cfFedId_Class> <cfFedId_Srv> <cfSrvId>5123451</cfSrvId> <cfClassId>eda2b2e2-34c5-11e1-b86c-0800200c9a66</cfClassId> <cfClassSchemeId>5a270628-f593-4ff4-a44a-95660c76e182</cfClassSchemeId> </cfFedId_Srv> </cfFedId> </cfResPubl> <cfPers> <cfPersId>ibn-Pers-87220</cfPersId> <cfPersName_Pers> <cfPersNameId>ibn-PersName-87220-3</cfPersNameId> <cfClassId>55f90543-d631-42eb-8d47-d8d9266cbb26</cfClassId> <cfClassSchemeId>7375609d-cfa6-45ce-a803-75de69abe21f</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> <cfFamilyNames>Kamal</cfFamilyNames> <cfFirstNames>Maud</cfFirstNames> </cfPersName_Pers> </cfPers> <cfPers> <cfPersId>ibn-Pers-87221</cfPersId> <cfPersName_Pers> <cfPersNameId>ibn-PersName-87221-3</cfPersNameId> <cfClassId>55f90543-d631-42eb-8d47-d8d9266cbb26</cfClassId> <cfClassSchemeId>7375609d-cfa6-45ce-a803-75de69abe21f</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> <cfFamilyNames>Lameiras</cfFamilyNames> <cfFirstNames>Sonia</cfFirstNames> </cfPersName_Pers> </cfPers> <cfPers> <cfPersId>ibn-Pers-32816</cfPersId> <cfPersName_Pers> <cfPersNameId>ibn-PersName-32816-3</cfPersNameId> <cfClassId>55f90543-d631-42eb-8d47-d8d9266cbb26</cfClassId> <cfClassSchemeId>7375609d-cfa6-45ce-a803-75de69abe21f</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> <cfFamilyNames>Самец</cfFamilyNames> <cfFirstNames>Н.</cfFirstNames> </cfPersName_Pers> </cfPers> <cfPers> <cfPersId>ibn-Pers-93022</cfPersId> <cfPersName_Pers> <cfPersNameId>ibn-PersName-93022-3</cfPersNameId> <cfClassId>55f90543-d631-42eb-8d47-d8d9266cbb26</cfClassId> <cfClassSchemeId>7375609d-cfa6-45ce-a803-75de69abe21f</cfClassSchemeId> <cfStartDate>2021-02-16T24:00:00</cfStartDate> <cfFamilyNames>Noi</cfFamilyNames> <cfFirstNames>Autori</cfFirstNames> </cfPersName_Pers> </cfPers> <cfSrv> <cfSrvId>5123451</cfSrvId> <cfName cfLangCode='en' cfTrans='o'>CrossRef DOI prefix service</cfName> <cfDescr cfLangCode='en' cfTrans='o'>The service of issuing DOI prefixes to publishers</cfDescr> <cfKeyw cfLangCode='en' cfTrans='o'>persistent identifier; Digital Object Identifier</cfKeyw> </cfSrv> </CERIF>