A METHYLATION CLASSIFIER FOR DETECTION OF HPV-INDUCED INVASIVE CANCERS, NONHPV- INDUCED GYNAECOLOGICAL AND ANOGENITAL CANCERS AND THEIR HIGH-GRADE PRECURSOR LESIONS

摘要

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 13 September 2018 (13.09.2018) WIP0 I PCT omit VIII °nolo VIII 100 mil loon Imo oimIE (10) International Publication Number WO 2018/164577 Al (51) International Patent Classification: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, C12Q 1/6886 (2018.01) KM, ML, MR, NE, SN, TD, TG). (21) International Application Number: PCT/NL2018/050143 (22) International Filing Date: 09 March 2018 (09.03.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 17160346.7 10 March 2017 (10.03.2017) EP (71) Applicant: SELF-SCREEN B.V. [NL/NL]; Biothof 15 1, 1098 RX Amsterdam (NL). (72) Inventors: MEIJER, Christophorus Johannes Lamber- tus Maria; c/o Biothof 15 1, 1098 RX Amsterdam (NL). STEENBERGEN, Renske Daniela Maria; c/o Biothof 15 1, 1098 RX Amsterdam (NL). SNIJDERS, Petrus Jose- phus Ferdinandus; c/o Biothof 15 1, 1098 RX Amsterdam (NL). HEIDEMAN, Danielle Anne Marie; c/o Biothof 15 1, 1098 RX Amsterdam (NL). (74) Agent: JANSEN, C.M.; V.O., Carnegieplein 5, 2517 KJ Den Haag (NL). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Published: — with international search report (Art. 21(3)) 1-1 (54) Title: A METHYLATION CLASSIFIER FOR DETECTION OF HPV-INDUCED INVASIVE CANCERS, NONHPV- IN- DUCED GYNAECOLOGICAL AND ANOGENITAL CANCERS AND THEIR HIGH-GRADE PRECURSOR LESIONS IN (57) : The invention relates to method for detecting HPV-induced high-grade precancerous lesions, HPV-induced invasive 11 71- cancers and nonHPV-induced gynaecological and anogenital cancers, said method comprising detection of a methylation classifier consisting of the genes LHX8, ASCL1 and ST6GALNAC5 and their regulatory sequence in a cell whereby such hypermethylation 1-1 ---, indicates the presence of HPV- induced precursor lesions with invasive potential, HPV-induced invasive cancers and nonHPV-induced gynaecological and anogenital cancers. The invention further comprises the use of the methylation classifier consisting of genes LHX8, 1-1 ASCL1 and ST6GALNAC5 and their regulatory sequence in such a method and a test kit for the detection of LHX8. ASCL1 and/or ST6GALNAC5 methylation.