Digital Commons Network^™

Mutational Patterns In Chemotherapy Resistant Muscle-Invasive Bladder Cancer., David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y.T. Chen, R. Katherine Alpaugh, Jean Hoffman-Censits, Levi A. Garraway, Gad Getz, Scott L. Carter, Joaquim Bellmunt, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen

Department of Medical Oncology Faculty Papers

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts …

Crossed Aphasia In A Patient With Anaplastic Astrocytoma Of The Non-Dominant Hemisphere, Stephanie Prater, Neil Anand, Lawrence Wei, Neil Horner

Student Papers, Posters & Projects

Aphasia describes a spectrum of speech impairments due to damage in the language centers of the brain. Insult to the inferior frontal gyrus of the dominant cerebral hemisphere results in Broca's aphasia - the inability to produce fluent speech. The left cerebral hemisphere has historically been considered the dominant side, a characteristic long presumed to be related to a person's "handedness". However, recent studies utilizing fMRI have shown that right hemispheric dominance occurs more frequently than previously proposed and despite a person's handedness. Here we present a case of a right-handed patient with Broca's aphasia caused by a right-sided brain …

Molecular-Based Recursive Partitioning Analysis Model For Glioblastoma In The Temozolomide Era: A Correlative Analysis Based On Nrg Oncology Rtog 0525., Erica Hlavin Bell, Stephanie L Pugh, Joseph P. Mcelroy, Mark R. Gilbert, Minesh Mehta, Alexander C Klimowicz, Anthony Magliocco, Markus Bredel, Pierre Robe, Anca L. Grosu, Roger Stupp, Walter Curran, Aline P. Becker, Andrea L. Salavaggione, Jill S. Barnholtz-Sloan, Kenneth Aldape, Deborah T. Blumenthal, Paul D. Brown, Jon Glass, Luis Souhami, R. Jeffrey Lee, David Brachman, John Flickinger, Minhee Won, Arnab Chakravarti

Department of Neurosurgery Faculty Papers

Importance: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era.

Objective: To refine the existing clinically based recursive partitioning analysis (RPA) model by incorporating molecular variables.

Design, Setting, and Participants: NRG Oncology RTOG 0525 specimens (n = 452) were analyzed for protein biomarkers representing key pathways in GBM by a quantitative molecular microscopy-based approach with semiquantitative immunohistochemical validation. Prognostic significance of each protein was examined by single-marker and multimarker Cox regression analyses. To reclassify the prognostic risk groups, significant protein biomarkers on single-marker analysis were incorporated into an RPA model …