Citations 4
Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes
Doran, Graeme, Cheung, Tak-Hong, Yim, So‐Fan, Yu, Mei‐Yung, Thorner, Aaron R. , Pedamallu, Chandra Sekhar , Lau, Kei-Man, Ducar, Matthew D. , Wong, Raymond R.Y., Wang, Vivian W., Nag, Anwesha , Wollison, Bruce M. , Dalgarno, Audrey, Lee, Jacqueline Ho Sze , Yeung, Suet-Ying, Wong, Lo , Leung, Shuk-On A., Mu, Yi , Mok, Samuel C. , Crum, Christopher P. , Chiu, Rossa W. K. , Berkowitz, Ross S. , Wong, Yick‐Fu, Thorner, Aaron R , Ducar, Matthew D , Lee, Jacqueline H S , Mok, Samuel C , Chung, Tony K.H. , Yim, So Fan, Worley, Michael J. , Elias, Kevin M. , Ojesina, Akinyemi I. , Yeung, Suet Ying, Horowitz, Neil S. , Davis, Michelle , Leung, Shuk On Annie , Chan, Paul K.S. , Lawrence, Michael S.
Cancers | June 28, 2021 | Volume: 13 | Issue: 13 | Pages: 3218
Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.
Activating genomic mutations in the mTOR pathway to predict responses to everolimus and temsirolimus in patients with metastatic renal cell carcinoma (mRCC): Results from a large multi-institutional cohort.
Fay, André P. , Gray, Kathryn P. , Song, Jiaxi , Barrios, Pablo M. , Albigès, Laurence , Krajewski, Katherine M. , Pal, Sumanta K. , Heng, Daniel Yick Chin, Kwiatkowski, David J. , Thorner, Aaron R. , Rini, Brian I. , Agarwal, Neeraj , Ho, Thai H. , Van Allen, Eliezer M , Porta, Camillo , Bellmunt, Joaquim , McDermott, David F. , Signoretti, Sabina , Choueiri, Toni K.
Journal of Clinical Oncology | March 7, 2019 | Volume: 33 | Issue: 15_suppl | Pages: 4519-4519
Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma
Choueiri, Toni K. , Fay, André P. , Velasco, Guillermo de , Tyburczy, Magdalena E. , Hamieh, Lana , Albigès, Laurence , Ho, Thai H. , Song, Jiaxi , Pignon, Jean‐Christophe , Barrios, Pablo M. , Michaelson, M. Dror , Krajewski, Katherine M. , Porta, Camillo , Pal, Sumanta K. , Heng, Daniel Y.C., Gray, Kathryn P. , Kwiatkowski, David J. , Rini, Brian I. , Thorner, Aaron R. , Agarwal, Neeraj , Van Allen, Eliezer M , Bellmunt, Joaquim , McDermott, David F. , Signoretti, Sabina , Ho, Thai , Choueiri, Toni K
Clinical Cancer Research | February 1, 2016 | Volume: 22 | Issue: 10 | Pages: 2445-2452
Abstract Purpose: We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC). Experimental Design: We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for mutations using targeted next-generation sequencing of 560 cancer genes. Responders were defined as those with partial response (PR) by RECIST v1.0 or stable disease with any tumor shrinkage for 6 months or longer. Nonresponders were defined as those with disease progression during the first 3 months of therapy. Fisher exact test assessed the association between mutation status in mTOR pathway genes and treatment response. Results: Mutations in MTOR, TSC1, or TSC2 were more common in responders, 12 (28%) of 43, than nonresponders, 4 (11%) of 36 (P = 0.06). Mutations in TSC1 or TSC2 alone were also more common in responders, 9 (21%), than nonresponders, 2(6%), (P = 0.05). Furthermore, 5 (42%) of 12 subjects with PR had mutations in MTOR, TSC1, or TSC2 compared with 4 (11%) of 36 nonresponders (P = 0.03). Eight additional non-mTOR pathway genes were found to be mutated in at least 4 of 79 tumors (5%); none were associated positively with response. Conclusions: In this cohort of mRCC patients, mutations in MTOR, TSC1, or TSC2 were more common in patients who experienced clinical benefit from rapalogs than in those who progressed. However, a substantial fraction of responders (24 of 43, 56%) had no mTOR pathway mutation identified. Clin Cancer Res; 22(10); 2445–52. ©2016 AACR. See related commentary by Voss and Hsieh, p. 2320
Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women
Chung, Tony K.H. , Hummelen, Paul Van , Chan, Paul K.S. , Cheung, Tak Hong , Yim, So Fan, Yu, Mei , MacConaill, Laura E. , Doran, Graeme, Pedamallu, Chandra Sekhar , Ojesina, Akinyemi I. , Wong, Raymond R.Y., Wang, Vivian W., Freeman, Samuel S. , Lau, Tat‐San , Kwong, Joseph , Chan, Loucia Kit Ying , May, Taymaa , Esselen, Katharine M. , Elias, Kevin M. , Smith, David I., Crum, Christopher P. , Meyerson, Matthew , Berkowitz, Ross S. , Wong, Yick Fu, Ducar, Matthew D. , Thorner, Aaron R. , Fromer, Menachem , Worley, Michael J. , Lawrence, Michael S. , Getz, Gad , Smith, David I., Elias, Kevin M
International Journal of Cancer | January 28, 2015 | Volume: 137 | Issue: 4 | Pages: 776-783