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Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence.

Christian Righini 1 Florence de Fraipont 2 Jean-François Timsit 3 Claire Faure 4 Elisabeth Brambilla 5 Emile Reyt 6 Marie-Christine Favrot 2
1 INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon)
Service d'ORL et de chirurgie cervicale, INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble, UF cancérologie biologique et biothérapie
2 INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon)
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble, UF cancérologie biologique et biothérapie
3 INSERM U823, équipe 11 (Epidémiologie des cancers et des affections graves)
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
5 INSERM U823, équipe 2 (Bases Moléculaires de la Progression des Cancers du Poumon)
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble, Département d'anatomie et cythologie pathologique
Abstract : PURPOSE: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse. EXPERIMENTAL DESIGN: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series. RESULTS: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in >75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed. CONCLUSIONS: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.
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https://www.hal.inserm.fr/inserm-00173060
Contributor : Danielle Salas <>
Submitted on : Tuesday, September 18, 2007 - 4:57:10 PM
Last modification on : Friday, November 6, 2020 - 4:13:24 AM

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Christian Righini, Florence de Fraipont, Jean-François Timsit, Claire Faure, Elisabeth Brambilla, et al.. Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence.. Clinical Cancer Research, American Association for Cancer Research, 2007, 13 (4), pp.1179-85. ⟨10.1158/1078-0432.CCR-06-2027⟩. ⟨inserm-00173060⟩

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