MISSION

45, NPV = 8%), 3 months (n = 42, NPV = 79%), and 6 months (n = 46, NPV = 91%) post-induction. The
NPV increases to 88% when combining results from baseline and 6 weeks (n=16) and 92% when combining
baseline, 6 weeks and 3 months (n = 13). When reviewing results independently for positive predictive
value (PPV) at baseline, 6 weeks, 3 months, and 6 months, the results respectively are 35% (n = 66), 47%
(n = 43), 47% (n = 43), and 43% (n = 21). When combining baseline and 6 week results there is a PPV of
39% (n = 38); and combining baseline, 6 week and 3 month results gives a PPV of 52% (n = 23). A negative
FISH at baseline and 6 weeks after induction of therapy predicts tumor-free status although further
follow-up is required before definitive conclusions can be drawn.
FAMRI Supported Publications
Fomenkov A, Zangen R, Huang Y-P, Osada M, Guo Z, Fomenkov T, Trink B, Sidransky D, Ratovitski
EA. RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous
cell carcinoma cells upon DNA damage. Cell Cycle 2004;3:1285-1295.
Guo Z, Linn JF, Wu G, Anzick SL, Eisenberger CF, Halachmi S, Cohen Y, Fomenkov A, Hoque MO,
Okami K, Steiner G, Engles JM, Osada M, Moon C, Ratovitski E, Trent JM, Meltzer PS, Westra WH,
Kiemeney LA, Schoenberg MP, Sidransky D, Trink B. CDC91L1 (PIG-U) is a newly discovered oncogene
in human bladder cancer. Nat Med 2004;10:374-381.
Huang YP, Kim Y, Li Z, Fomenkov T, Fomenkov A, Ratovitski E. AEC-associated p63 mutations lead to
alternative splicing/protein stabilization of p63 and modulation of notch signaling. Cell Cycle
2005;4:1440-1447.
Huang YP, Wu G, Guo Z, Osada M, Fomenkov T, Park HL, Trink B, Fomenkov A, Ratovitski EA.
Altered sumoylation of p63a contributes to the split-hand/foot malformation phenotype. Cell Cycle
2004;3:1587-1596.
Wu G, Osada M, Guo Z, Fomenkov A, Begum S, Zhao M, Upadhyay S, Xing M, Wu F, Moon C, Westra
WH, Koch WM, Mantovani R, Califano JA, Ratovitski E, Sidransky D, Trink B. DeltaNp63alpha upregulates
the Hsp70 gene in human cancer. Cancer Res 2005;65:758-766.
GENETIC AND EPIGENETIC ALTERATIONS IN BLADDER CANCER BY TOBACCO SMOKE
Mohammad O. Hoque, DDS, PhD; The Johns Hopkins University; YCSA 2006
Many of the toxins that enter the body after inhalation of cigarette smoke are absorbed into the bloodstream
and excreted by the kidneys into the urine. Because urine stays in the bladder for hours before it is
expelled, the bladder epithelium is exposed to prolonged contact with carcinogens absorbed from smoke.
Recent evidence indicates that methylation and allelic deletion occur more frequently in cancers from
smokers than non-smokers. These observations suggest that a useful tobacco signature could emerge from
distinctive patterns of methylation and deletion. The objective of this study is to determine whether there
are distinct patterns of chromosomal loss and methylation in smokers and non-smokers. The discovery of
such patterns would be useful in the identification of bladder cancer-associated tumor suppressor genes.
Additionally, these genes can be used for overall clinical management of bladder cancer patients such as initial
diagnosis and monitoring of disease using urine sediment. To date, Dr. Hoque has been able to
demonstrate that methylation of a panel of genes can be used for diagnosis of bladder cancer, using urine
sediment. He also reported that stratification of tumor stage could be possible by profiling methylation
markers. By a multivariate analysis, Dr. Hoque reported that tissue inhibitor of metalloproteinases-3
methylation was an independent prognostic factor for bladder cancer survival with stage and metastasis (p
= 0.001 and 0.02, respectively). An integrated genetic and epigenetic approach will be continued for the
discovery of new genes, which should provide important insights into the pathogenesis of this tobaccorelated
cancer, and will provide information to develop strategies for early detection and treatment.
FAMRI Supported Publications
Hoque MO, Kim MS, Ostrow KL, Liu J, Wisman BA, Park HL, Poeta ML, Jeronimo C, Henrique R,
Lendvai A, Schuuring ED, Begum S, Rosenbaum R, Ongenaert M, Yamashita K, Califano J, Westra
WH, Zee VD, Criekinge WV, Sidransky D. Genome-wide promoter analysis uncovers portions of the
cancer methylome. Cancer Res 2008;68(8):2661-70.
Dasgupta S, Hoque MO, Upadhyay S, Sidransky D. Mitochondria encoded cytochrome B mutation promotes
tumor growth in bladder cancer through NFkB2 activation. Cancer Res 2008;68:700-706.
Hoque MO, Begum S, Brait M, Jeronimo C, Ostrow K, Trock B, Westra WH, Schoenberg M, Sidransky
D. TIMP3 promoter methylation is an independent prognostic factor for bladder cancer. J Urol
2008;179(2):743-7.
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