Toward the molecular dissection of peritoneal pseudomyxoma

F Pietrantonio, F Perrone, Alessia Mennitto, E M Gleeson, M Milione, E Tamborini, A Busico, G Settanni, R Berenato, M Caporale, F Morano, I Bossi, A Pellegrinelli, M Di Bartolomeo, F de Braud, D Baratti, W B Bowne, S Kusamura, M Deraco

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Abstract

BACKGROUND: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even after adjusting for clinico-pathological prognostic variables. The identification of additional prognostic or even predictive biomarkers is an unmet clinical need.

PATIENTS AND METHODS: Forty patients with mucinous appendiceal tumors and PMP were clinically eligible and had evaluable tumor samples obtained after CRS and HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal Genome Machine platform (Life Technologies).

RESULTS: KRAS and GNAS mutations were found in 72% and 52%, and their allelic frequency was below 10% in 55% and 43% of samples, respectively. KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS mutations were independently associated with PFS (P = 0.012); GNAS mutations were not-being significantly associated with other poor prognostic features such as incomplete cytoreduction or KRAS mutations. Validation of results was carried out in an independent bi-institutional cohort of 25 patients and the prognostic effect of KRAS mutations was again confirmed in the multivariate model (P = 0.029). NGS approach allowed the discovery of other potentially druggable mutations such as those in PI3K, AKT, LKB1, FGFR3 and PDGFRA.

CONCLUSIONS: Given the homogeneity of this series and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the first time a poor prognostic role of KRAS mutations.

Original languageEnglish
Pages (from-to)2097-2103
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 2016

Keywords

  • Journal Article

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    Pietrantonio, F., Perrone, F., Mennitto, A., Gleeson, E. M., Milione, M., Tamborini, E., Busico, A., Settanni, G., Berenato, R., Caporale, M., Morano, F., Bossi, I., Pellegrinelli, A., Di Bartolomeo, M., de Braud, F., Baratti, D., Bowne, W. B., Kusamura, S., & Deraco, M. (2016). Toward the molecular dissection of peritoneal pseudomyxoma. Annals of Oncology, 27(11), 2097-2103. https://doi.org/10.1093/annonc/mdw314