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A. Montero

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    MINI 38 - Biology and Prognosis (ID 167)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI38.03 - Validation of a Specific Missense GTF2I Mutation in More Indolent Thymic Epithelial Tumours (ID 3017)

      18:30 - 20:00  |  Author(s): A. Montero

      • Abstract
      • Presentation
      • Slides

      Thymic epithelial tumours (TETs) are rare intrathoracic cancers that can be invasive and very difficult to treat. There is currently a huge gap in the understanding of the basic science behind their development as well as great clinical need for development of effective treatments. Recently a missense mutation (T>A, at the same position on chromosome 7, 74146970) was identified in GTF2I at high frequency (78%) in the more indolent type A and AB thymomas. We examined the frequency of this alteration in an independent cohort of well clinically characterized patients from the UK.

      Tumour samples were collected from 94 patients from a single tertiary cardiothoracic centre in the UK, the Royal Brompton & Harefield NHS Foundation Trust (London). These were subject to histological assessment by expert Consultant Histopathologists to confirm the diagnosis and determine tumour abundance. DNA was extracted with Quiagen’s QIAamp DNA FFPE Tissue Kit (Catalogue No. 56404). PCR and Sanger sequencing was performed with semi-nested primers.

      We assessed the frequency of the GTF2I mutation in a total of 94 TETs with a tumour abundance of at least 70%. The mean age for all patients was 57 and the male: female ratio was 1:1.25 The GTF2I mutation was seen in 25 of 87 evaluable TETs (29%) and was present more commonly in type A (85%) and AB (46%) thymomas. The frequency decreased to 9% in type B1 (1/11) and 5% in type B2 thymomas (1/19). In our cohort the mutation was not detected in any B3 thymomas or carcinomas, including neuroendocrine tumours or two cases of thymic hyperplasia. Interestingly all AB thymomas with the mutation had a much lower percentage of mutant alleles compared to the majority of the A thymomas. Twenty-three of the 25 patients (92%) with the mutation had Stage I – II disease at presentation and had complete resection of their thymoma.

      Our results confirm the presence of the GTF2I mutation at a high frequency in type A and AB thymomas in an entirely different patient cohort. Although the frequency of the mutation in type A thymomas in our cohort is very similar to what was reported originally (85% and 82% respectively) it was lower in the AB thymomas (46% and 74% respectively). Explanations for this include the smaller sample number in our cohort and a higher percentage of the lymphocytic component in our samples than that in the original series. The lower mutation frequency in the B subtypes and carcinomas compared to the original series could be due to the smaller numbers in our cohort. We aim to address these issues by expanding our validation series to over 200 samples. Whole exome and RNA sequencing of TETs is ongoing and will allow us to further confirm and extend this finding.

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