[904] Clinical Implications of Selected Somatic Mutations in the Recurrence of Invasive Urothelial Carcinomas

O Lin, D Solit, H Al-Ahmadie, A Heguy, VE Reuter, N Ishill, M Milowsky. Memorial Sloan-Kettering Cancer Center, New York

Background: Urothelial carcinoma is a common malignancy with a variable biology and natural history. The majority of patients are initially diagnosed with superficial cancer, however, 20-40% of patients either present with more advanced disease or progress after therapy for early stage disease. Genetic mutations are frequent in urothelial carcinomas and maybe associated with clinical outcome. Prior studies have shown that the most common somatic mutations in urothelial carcinomas, independent of grade, are FGFR3, RB1, PIK3CA, CDKN2A and HRAS. This study analyzes the correlation of somatic mutations and recurrence interval in invasive urothelial carcinomas.
Design: Frozen material from 56 cystectomy specimens with invasive urothelial carcinomas were retrieved from our institution tumor bank for analysis. Only cases with matched pair of tumor and normal tissue were included in this study. DNA was extracted from these specimens and submitted to Sanger Sequencing for FGFR3, RB1, PIK3CA,CDKN2A and HRAS and BRAF. PCR reactions were carried out with 10 ng of whole genome amplified DNA. All putative mutations were confirmed by a second PCR and sequencing reaction, in parallel with amplification and sequencing of matched normal tissue DNA. All traces for mutation calls were manually reviewed.
Results: Result: Of the 56 patients analyzed there were 32 recurrences with a median time to recurrence of 18 months. The table below summarizes the findings.

MutationNRecurrenceMedian Time to Recurrence (95% CI)PValue
FGFR3
Mutated21100.85
Wild Type543118 (13 - 35)
BRAF
Mutated3216 (10 - 16)0.45
Wild Type533020 (13 - 38)
PIK3CA
Mutated52Not reached0.44
Wild Type513018 (13 - 35)
TP 53
Mutated83Not reached0.28
Wild Type483917 (13 - 35)
RB
Mutated2217 (17 - 18)0.59
Wild Type543020 (13 - 36)
CDKN2A
Mutated228 (7 - 9)0.0005
Wild Type543020 (14 - 36)



Conclusions: CDKN2A mutations appear associated with shorter recurrence interval in patients with invasive urothelial carcinomas. The other mutations analyzed do not appear to correlate with earlier recurrence.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 142, Wednesday Afternoon

 

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