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Ly, Amy

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Ly

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Amy

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Ly, Amy
Author's Publications: search.filters.isAuthorOfPublication.6df4687f-c75b-4187-b061-1342925a43df

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    Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer
    (2014) Lohr, Jens; Adalsteinsson, Viktor A.; Cibulskis, Kristian; Choudhury, Atish; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua; Zhang, Cheng-Zhong; Shalek, Alex K.; Satija, Rahul; Trombetta, John T.; Lu, Diana; Tallapragada, Naren; Tahirova, Narmin; Kim, Sora; Blumenstiel, Brendan; Sougnez, Carrie; Lowe, Alarice; Wong, Bang; Auclair, Daniel; Van Allen, Eliezer; Nakabayashi, Mari; Lis, Rosina T.; Lee, Gwo-Shu M.; Li, Tiantian; Chabot, Matthew S.; Ly, Amy; Taplin, Mary-Ellen; Clancy, Thomas; Loda, Massimo; Regev, Aviv; Meyerson, Matthew; Hahn, William; Kantoff, Philip; Golub, Todd; Getz, Gad; Boehm, Jesse S.; Love, J. Christopher
    Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two prostate cancer patients including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early-trunk and 56 metastatic-trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.
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    Blocking the formation of radiation–induced breast cancer stem cells
    (Impact Journals LLC, 2014) Wang, YangYang; Li, Wende; Patel, Shalin; Cong, Juan; Zhang, Nan; Sabbatino, Francesco; Liu, Xiaoyan; Qi, Yuan; Huang, Peigen; Lee, Hang; Taghian, Alphonse; Li, Jian-Jian; DeLeo, Albert B.; Ferrone, Soldano; Epperly, Michael W.; Ferrone, Cristina; Ly, Amy; Brachtel, Elena; Wang, Xinhui
    The goal of adjuvant (post-surgery) radiation therapy (RT) for breast cancer (BC) is to eliminate residual cancer cells, leading to better local tumor control and thus improving patient survival. However, radioresistance increases the risk of tumor recurrence and negatively affects survival. Recent evidence shows that breast cancer stem cells (BCSCs) are radiation-resistant and that relatively differentiated BC cells can be reprogrammed into induced BCSCs (iBCSCs) via radiation-induced re-expression of the stemness genes. Here we show that in irradiation (IR)-treated mice bearing syngeneic mammary tumors, IR-induced stemness correlated with increased spontaneous lung metastasis (51.7%). However, IR-induced stemness was blocked by targeting the NF-κB- stemness gene pathway with disulfiram (DSF)and Copper (Cu2+). DSF is an inhibitor of aldehyde dehydrogenase (ALDH) and an FDA-approved drug for treating alcoholism. DSF binds to Cu2+ to form DSF-Cu complexes (DSF/Cu), which act as a potent apoptosis inducer and an effective proteasome inhibitor, which, in turn, inhibits NF-κB activation. Treatment of mice with RT and DSF significantly inhibited mammary primary tumor growth (79.4%) and spontaneous lung metastasis (89.6%) compared to vehicle treated mice. This anti-tumor efficacy was associated with decreased stem cell properties (or stemness) in tumors. We expect that these results will spark clinical investigation of RT and DSF as a novel combinatorial treatment for breast cancer.
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    Prediction of primary breast cancer size and T-stage using micro-computed tomography in lumpectomy specimens
    (Medknow, 2015) Sarraj, WafaM; Tang, Rong; Najjar, Anas L; Griffin, Molly; Bui, Anthony H; Zambeli-Ljepovic, Alan; Senter-Zapata, Mike; Lewin-Berlin, Maya; Fernandez, Leopoldo; Buckley, Juliette; Ly, Amy; Brachtel, Elena; Aftreth, Owen; Gilbertson, John R; Yagi, Yukako; Gadd, Michele; Hughes, Kevin; Smith, BarbaraL; Michaelson, JamesS
    Background: Histopathology is the only accepted method to measure and stage the breast tumor size. However, there is a need to find another method to measure and stage the tumor size when the pathological assessment is not available. Micro-computed tomography. (micro-CT) has the ability to measure tumor in three dimensions in an intact lumpectomy specimen. In this study, we aimed to determine the accuracy of micro-CT to measure and stage the primary tumor size in breast lumpectomy specimens, as compared to the histopathology. Materials and Methods: Seventy-two women who underwent lumpectomy surgery at the Massachusetts General Hospital Department of Surgery from June 2011 to September 2011, and from August 2013 to December 2013 participated in this study. The lumpectomy specimens were scanned using micro-CT followed by routine pathological processing. The maximum dimension of the invasive breast tumor was obtained from the micro-CT image and was compared to the corresponding pathology report for each subject. Results: The invasive tumor size measurement by micro-CT was underestimated in 24 cases. (33%), overestimated in 37 cases. (51%), and matched it exactly in 11 cases. (15%) compared to the histopathology measurement for all the cases. However, micro-CT T-stage classification differed from histopathology in only 11. (15.2%) with 6 cases. (8.3%) classified as a higher stage by micro-CT, and 5 cases. (6.9%) classified as lower compared to histopathology. In addition, micro-CT demonstrated a statically significant strong agreement (κ =0.6, P < 0.05) with pathological tumor size and staging for invasive ductal carcinoma. (IDC) group. In contrast, there was no agreement. (κ = −2, P = 0.67) between micro-CT and pathology in estimating and staging tumor size for invasive lobular carcinoma. (ILC) group. This could be explained by a small sample size. (7) for ILC group. Conclusions: Micro-CT is a promising modality for measuring and staging the IDC.