المؤلفون: Ramachandran, Dhanya, Tyrer, Jonathan P, Kommoss, Stefan, DeFazio, Anna, Riggan, Marjorie J, Webb, Penelope M, Fasching, Peter A, Lambrechts, Diether, García, María J, Rodríguez-Antona, Cristina, Goodman, Marc T, Modugno, Francesmary, Moysich, Kirsten B, Karlan, Beth Y, Lester, Jenny, Kjaer, Susanne K, Jensen, Allan, Høgdall, Estrid, Goode, Ellen L, Cliby, William A, Kumar, Amanika, Wang, Chen, Cunningham, Julie M, Winham, Stacey J, Monteiro, Alvaro N, Schildkraut, Joellen M, Cramer, Daniel W, Terry, Kathryn L, Titus, Linda, Bjorge, Line, Thomsen, Liv Cecilie Vestrheim, Pejovic, Tanja, Høgdall, Claus K, McNeish, Iain A, May, Taymaa, Huntsman, David G, Pfisterer, Jacobus, Canzler, Ulrich, Park-Simon, Tjoung-Won, Schröder, Willibald, Belau, Antje, Hanker, Lars, Harter, Philipp, Sehouli, Jalid, Kimmig, Rainer, de Gregorio, Nikolaus, Schmalfeldt, Barbara, Baumann, Klaus, Hilpert, Felix, Burges, Alexander, Winterhoff, Boris, Schürmann, Peter, Speith, Lisa-Marie, Hillemanns, Peter, Berchuck, Andrew, Johnatty, Sharon E, Ramus, Susan J, Chenevix-Trench, Georgia, Pharoah, Paul DP, Dörk, Thilo, Heitz, Florian

المصدر: npj Genomic Medicine. 9(1)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Ovarian Cancer, Clinical Research, Cancer, Rare Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, AOCS Group, OPAL Study Group, Medical biotechnology

الوصف: Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/93s7f8gsTest

المؤلفون: O’Mahony, Denise G, Ramus, Susan J, Southey, Melissa C, Meagher, Nicola S, Hadjisavvas, Andreas, John, Esther M, Hamann, Ute, Imyanitov, Evgeny N, Andrulis, Irene L, Sharma, Priyanka, Daly, Mary B, Hake, Christopher R, Weitzel, Jeffrey N, Jakubowska, Anna, Godwin, Andrew K, Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A, Mai, Phuong L, Claes, Kathleen BM, Teixeira, Manuel R, Chung, Wendy K, Lazaro, Conxi, Hulick, Peter J, Toland, Amanda E, Pedersen, Inge Sokilde, Neuhausen, Susan L, Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A, Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L, Domchek, Susan M, Osorio, Ana, García, María J, Karlan, Beth Y, De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T, Dörk, Thilo, Speith, Lisa-Marie, dos Santos, Elizabeth Santana, da Costa, Alexandre André BA, Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K, Wappenschmidt, Barbara, Easton, Douglas F, Tischkowitz, Marc, Singer, Christian F, Tan, Yen Yen, Whittemore, Alice S, Sieh, Weiva, Brenton, James D, Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul DP, Antoniou, Antonis C, Goldgar, David E, Spurdle, Amanda B, Michailidou, Kyriaki

المصدر: British Journal of Cancer. 128(12)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Breast Cancer, Genetics, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Female, Virulence, BRCA1 Protein, BRCA2 Protein, Ovarian Neoplasms, Genetic Predisposition to Disease, Breast Neoplasms, HEBON Investigators, GEMO Study Collaborators, AOCS Group, CZECANCA Consortium, Consortium of Investigators of Modifiers of BRCA1/2, Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis

الوصف: BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/40j9s31tTest

المؤلفون: O'Mahony, Denise G., Ramus, Susan J., Southey, Melissa C., Meagher, Nicola S., Hadjisavvas, Andreas, John, Esther M., Hamann, Ute, Imyanitov, Evgeny N., Andrulis, Irene L., Sharma, Priyanka, Daly, Mary B., Hake, Christopher R., Weitzel, Jeffrey N., Jakubowska, Anna, Godwin, Andrew K., Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A., Mai, Phuong L., Claes, Kathleen B. M., Teixeira, Manuel R., Chung, Wendy K., Lazaro, Conxi, Hulick, Peter J., Toland, Amanda E., Pedersen, Inge Sokilde, Neuhausen, Susan L., Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A., Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L., Domchek, Susan M., Osorio, Ana, Garcia, Maria J., Karlan, Beth Y., De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T., Doerk, Thilo, Speith, Lisa-Marie, dos Santos, Elizabeth Santana, da Costa, Alexandre Andre B. A., Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K., Wappenschmidt, Barbara, Easton, Douglas F., Tischkowitz, Marc, Singer, Christian F., Tan, Yen Yen, Whittemore, Alice S., Sieh, Weiva, Brenton, James D., Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul D. P., Antoniou, Antonis C., Goldgar, David E., Spurdle, Amanda B., Michailidou, Kyriaki, Mourits, Marian J. E., Lesueur, Fabienne

المساهمون: Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics

مصطلحات موضوعية: Germline mutations, Uncertain significance, Clinical-significance, Unknown significance, Sequence variants, Carcinoma, Recommendations, Frequency, Series, Classification, 3122 Cancers

الوصف: BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: O'Mahony , D G , Ramus , S J , Southey , M C , Meagher , N S , Hadjisavvas , A , John , E M , Hamann , U , Imyanitov , E N , Andrulis , I L , Sharma , P , Daly , M B , Hake , C R , Weitzel , J N , Jakubowska , A , Godwin , A K , Arason , A , Bane , A , Simard , J , Soucy , P , Caligo , M A , Mai , P L , Claes , K B M , Teixeira , M R , Chung , W K , Lazaro , C , Hulick , P J , Toland , A E , Pedersen , I S , Neuhausen , S L , Vega , A , de la Hoya , M , Nevanlinna , H , Dhawan , M , Zampiga , V , Danesi , R , Varesco , L , Gismondi , V , Vellone , V G , James , P A , Janavicius , R , Nikitina-Zake , L , Nielsen , F C , van Overeem Hansen , T , Pejovic , T , Borg , A , Rantala , J , Offit , K , Montagna , M , Nathanson , K L , Domchek , S M , Osorio , A , Garcia , M J , Karlan , B Y , De Fazio , A , Bowtell , D , McGuffog , L , Leslie , G , Parsons , M T , Doerk , T , Speith , L-M , dos Santos , E S , da Costa , A A B A , Radice , P , Peterlongo , P , Papi , L , Engel , C , Hahnen , E , Schmutzler , R K , Wappenschmidt , B , Easton , D F , Tischkowitz , M , Singer , C F , Tan , Y Y , Whittemore , A S , Sieh , W , Brenton , J D , Yannoukakos , D , Fostira , F , Konstantopoulou , I , Soukupova , J , Vocka , M , Chenevix-Trench , G , Pharoah , P D P , Antoniou , A C , Goldgar , D E , Spurdle , A B , Michailidou , K , Mourits , M J E & Lesueur , F 2023 , ' Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2 ' , British Journal of Cancer , vol. 128 , no. 12 , pp. 2283-2294 . https://doi.org/10.1038/s41416-023-02263-5Test; 47149927-466d-429f-a2f1-25649fdf6701; http://hdl.handle.net/10138/563694Test; 000989800600004

الإتاحة: http://hdl.handle.net/10138/563694Test

المؤلفون: O’Mahony, Denise G., Ramus, Susan J., Southey, Melissa C., Meagher, Nicola S., Hadjisavvas, Andreas, John, Esther M., Hamann, Ute, Imyanitov, Evgeny N., Andrulis, Irene L., Sharma, Priyanka, Daly, Mary B., Hake, Christopher R., Weitzel, Jeffrey N., Jakubowska, Anna, Godwin, Andrew K., Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A., Mai, Phuong L., Claes, Kathleen B.M., Teixeira, Manuel R., Chung, Wendy K., Lazaro, Conxi, Hulick, Peter J., Toland, Amanda E., Pedersen, Inge Sokilde, Mourits, Marian J.E., Neuhausen, Susan L., Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A., Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L., Domchek, Susan M., Osorio, Ana, García, María J., Karlan, Beth Y., Lesueur, Fabienne, De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T., Dörk, Thilo, Speith, Lisa Marie, dos Santos, Elizabeth Santana, da Costa, Alexandre André B.A., Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K., Wappenschmidt, Barbara, Easton, Douglas F., Tischkowitz, Marc, Singer, Christian F., Tan, Yen Yen, Whittemore, Alice S., Sieh, Weiva, Brenton, James D., Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul D.P., Antoniou, Antonis C., Goldgar, David E., Spurdle, Amanda B., Michailidou, Kyriaki

المصدر: O’Mahony , D G , Ramus , S J , Southey , M C , Meagher , N S , Hadjisavvas , A , John , E M , Hamann , U , Imyanitov , E N , Andrulis , I L , Sharma , P , Daly , M B , Hake , C R , Weitzel , J N , Jakubowska , A , Godwin , A K , Arason , A , Bane , A , Simard , J , Soucy , P , Caligo , M A , Mai , P L , Claes , ....

الوصف: Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Results: No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusions: We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management. ; Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods: Data for 10,373 ovarian cancer cases, including carriers and ...

وصف الملف: application/pdf

العلاقة: https://vbn.aau.dk/da/publications/27de752d-e9ee-49dc-b268-3c625ba13d89Test

الإتاحة: https://doi.org/10.1038/s41416-023-02263-5Test
https://vbn.aau.dk/da/publications/27de752d-e9ee-49dc-b268-3c625ba13d89Test
https://vbn.aau.dk/ws/files/538893737/s41416-023-02263-5.pdfTest
http://www.scopus.com/inward/record.url?scp=85153204607&partnerID=8YFLogxKTest

المؤلفون: O'Mahony, Denise G, Ramus, Susan J, Southey, Melissa C, Meagher, Nicola S, Hadjisavvas, Andreas, John, Esther M, Hamann, Ute, Imyanitov, Evgeny N, Andrulis, Irene L, Sharma, Priyanka, Daly, Mary B, Hake, Christopher R, Weitzel, Jeffrey N, Jakubowska, Anna, Godwin, Andrew K, Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A, Mai, Phuong L, Claes, Kathleen B M, Teixeira, Manuel R, Chung, Wendy K, Lazaro, Conxi, Hulick, Peter J, Toland, Amanda E, Pedersen, Inge Sokilde, Neuhausen, Susan L, Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A, Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L, Domchek, Susan M, Osorio, Ana, García, María J, Karlan, Beth Y, De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T, Dörk, Thilo, Speith, Lisa-Marie, Dos Santos, Elizabeth Santana, da Costa, Alexandre André B A, Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K, Wappenschmidt, Barbara, Easton, Douglas F, Tischkowitz, Marc, Singer, Christian F, Tan, Yen Yen, Whittemore, Alice S, Sieh, Weiva, Brenton, James D, Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul D P, Antoniou, Antonis C, Goldgar, David E, Spurdle, Amanda B, Michailidou, Kyriaki

المساهمون: O'Mahony, Denise G, Ramus, Susan J, Southey, Melissa C, Meagher, Nicola S, Hadjisavvas, Andrea, John, Esther M, Hamann, Ute, Imyanitov, Evgeny N, Andrulis, Irene L, Sharma, Priyanka, Daly, Mary B, Hake, Christopher R, Weitzel, Jeffrey N, Jakubowska, Anna, Godwin, Andrew K, Arason, Adalgeir, Bane, Anita, Simard, Jacque, Soucy, Penny, Caligo, Maria A, Mai, Phuong L, Claes, Kathleen B M, Teixeira, Manuel R, Chung, Wendy K, Lazaro, Conxi, Hulick, Peter J, Toland, Amanda E, Pedersen, Inge Sokilde, Neuhausen, Susan L, Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A, Janavicius, Ramuna, Nikitina-Zake, Liene, Nielsen, Finn Ciliu, van Overeem Hansen, Thoma, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L, Domchek, Susan M, Osorio, Ana, García, María J, Karlan, Beth Y, De Fazio, Anna, Bowtell, David, Mcguffog, Lesley, Leslie, Goska, Parsons, Michael T, Dörk, Thilo, Speith, Lisa-Marie, Dos Santos, Elizabeth Santana, da Costa, Alexandre André B A, Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K, Wappenschmidt, Barbara, Easton, Douglas F, Tischkowitz, Marc, Singer, Christian F, Tan, Yen Yen, Whittemore, Alice S, Sieh, Weiva, Brenton, James D, Yannoukakos, Drakouli, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul D P, Antoniou, Antonis C, Goldgar, David E, Spurdle, Amanda B, Michailidou, Kyriaki

الوصف: Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Results: No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusions: We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37076566; info:eu-repo/semantics/altIdentifier/wos/WOS:000989800600004; firstpage:1; lastpage:10; numberofpages:10; journal:BRITISH JOURNAL OF CANCER; https://hdl.handle.net/11567/1116975Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85153204607

الإتاحة: https://doi.org/10.1038/s41416-023-02263-5Test
https://hdl.handle.net/11567/1116975Test

المؤلفون: Polaczek, Rahel, Schürmann, Peter, Speith, Lisa-Marie, Geffers, Robert, Dürst, Matthias, Hillemanns, Peter, Park-Simon, Tjoung-Won, Liebrich, Clemens, Dörk, Thilo

المصدر: http://lobid.org/resources/99370679462806441Test#!, 13(1):146.

مصطلحات موضوعية: Female [MeSH], Ribonuclease H/genetics [MeSH], Ribonuclease H/metabolism [MeSH], MMR deficiency, Humans [MeSH], Progression-Free Survival [MeSH], Ovarian Neoplasms/enzymology [MeSH], Epithelial ovarian carcinoma, Homologous recombination, Middle Aged [MeSH], RNase H2, Brief Communication, Ovarian Neoplasms/genetics [MeSH], Platinum resistance, Germ-Line Mutation [MeSH], Ribonucleotide excision repair, Case-Control Studies [MeSH], Computational Biology/methods [MeSH], Ovarian Neoplasms/pathology [MeSH]

الوصف: Epithelial ovarian carcinoma (EOC) is a genetically heterogeneous disease that is partly driven by molecular defects in mismatch repair (MMR) or homology-directed DNA repair (HDR). Ribonuclease H2 serves to remove mis-incorporated ribonucleotides from DNA which alleviates HDR mechanisms and guides the MMR machinery. Although Ribonuclease H2 has been implicated in cancer, the role of germline variants for ovarian cancer is unknown. In the present case-control study, we sequenced the coding and flanking untranslated regions of the RNASEH2A, RNASEH2B and RNASEH2C genes, encoding all three subunits of Ribonuclease H2, in a total of 602 German patients with EOC and of 940 healthy females from the same population. We identified one patient with a truncating variant in RNASEH2B, p.C44X, resulting in a premature stop codon. This patient had high-grade serous EOC with an 8 years survival after platinum/taxane-based therapy. Subsequent analysis of TCGA data similarly showed a significantly longer progression-free survival in ovarian cancer patients with low RNASEH2B or RNASEH2C expression levels. In conclusion, loss-of-function variants in Ribonuclease H2 genes are not common predisposing factors in ovarian cancer but the possibility that they modulate therapeutic platinum response deserves further investigation.

العلاقة: https://repository.publisso.de/resource/frl:6463077Test; https://doi.org/10.1186/s13048-020-00753-1Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756920Test/

الإتاحة: https://doi.org/10.1186/s13048-020-00753-1Test
https://repository.publisso.de/resource/frl:6463077Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756920Test/

المؤلفون: Ramachandran, Dhanya, Schürmann, Peter, Mao, Qianqian, Wang, Yingying, Bretschneider, Lisa‐Marie, Speith, Lisa‐Marie, Hülse, Fabienne, Enßen, Julia, Bousset, Kristine, Jentschke, Matthias, Böhmer, Gerd, Strauß, Hans‐Georg, Hirchenhain, Christine, Schmidmayr, Monika, Tarbiat, Johanna, Runnebaum, Ingo, Dürst, Matthias, Hein, Alexander, Koch, Martin, Ruebner, Matthias, Ekici, Arif, Beckmann, Matthias W., Fasching, Peter A., Luyten, Alexander, Petry, Karl‐Ulrich, Hillemanns, Peter, Dörk, Thilo

مصطلحات موضوعية: ddc:610

الوصف: The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single‐nucleotide polymorphisms in a large case‐control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA‐DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79‐0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04‐1.31, P = .008) and with high‐grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70‐0.87, P = 7.1 × 10−6; rs2844511: OR 1.13, 95% CI 1.01‐1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75‐0.91, P = 6.9 × 10−5; rs2844511: OR 1.14, 95% CI 1.04‐1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low‐grade dysplasia (OR 1.26, 95% CI 1.04‐1.54, P = .019). In case‐only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA‐DQA1, suggesting extensive co‐regulation. All three genes were upregulated in HPV16‐positive samples. In stratified analyses, rs9272117 was associated with HLA‐DQA1 levels, specifically in HPV‐positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA‐DQA1. Altogether, our results support 6p21.32‐33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA‐DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.

وصف الملف: application/pdf

العلاقة: https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/15256Test; urn:nbn:de:bvb:29-opus4-152561; https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-152561Test; https://doi.org/10.1002/ijc.33171Test; https://opus4.kobv.de/opus4-fau/files/15256/IJC_IJC33171.pdfTest

الإتاحة: https://doi.org/10.1002/ijc.33171Test
https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/15256Test
https://nbn-resolving.org/urn:nbn:de:bvb:29-opus4-152561Test
https://opus4.kobv.de/opus4-fau/files/15256/IJC_IJC33171.pdfTest