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Publications [#134817] of Randy L. Jirtle

Papers Published

  1. TA Jamieson, DM Brizel, JK Killian, Y Oka, HS Jang, X Fu, RW Clough, RT Vollmer, MS Anscher, RL Jirtle, M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis., BMC cancer, England, vol. 3 (February, 2003), pp. 4, ISSN 1471-2407
    (last updated on 2003/09/18)

    BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.

    Adult • Aged • Carcinoma, Squamous Cell • Female • Genetic Predisposition to Disease • Head and Neck Neoplasms • Humans • Loss of Heterozygosity* • Male • Middle Aged • Receptor, IGF Type 2 • Survival Analysis • Treatment Failure • Treatment Outcome • genetics* • mortality • therapy*