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Poster session 18

1922P - Targeted resequencing designed specifically for thymic epithelial tumours confirmed the high prevalence of GTF2I mutations

Date

14 Sep 2024

Session

Poster session 18

Topics

Tumour Site

Thymoma and Thymic Cancer

Presenters

Iacopo Petrini

Citation

Annals of Oncology (2024) 35 (suppl_2): S1115-S1121. 10.1016/annonc/annonc1613

Authors

I. Petrini1, E. Pardini2, F. Cucchiara2, G. Sardo Infirri3, I.S. Burzi3, S. Barachini4, M. Monatli4, M. Maestri5, R. Ricciardi6, V. Nicolì3, F. Coppedè3, D. Bacchin7, F. Melfi7, V. Aprile7, M. Lucchi3

Author affiliations

  • 1 Translational Research And New Technologies In Medicine And Surgery Department, University of Pisa, 56126 - Pisa/IT
  • 2 Department Of Translational Research And Of New Surgical And Medical Technologies, University of Pisa, 56125 - PISA/IT
  • 3 Department Of Translational Research And Of New Surgical And Medical Technologies, University of Pisa, 56126 - Pisa/IT
  • 4 Department Of Clinical And Experimental Medicine, University of Pisa, 56126 - Pisa/IT
  • 5 U.o. Neurology, University of Pisa, 56126 - Pisa/IT
  • 6 U.o. Neurology, Azienda Ospedaliero Universitaria Pisana, 56126 - Pisa/IT
  • 7 Department Of Surgical, Medical And Molecular Pathology And Critical Care Medicine, University of Pisa, 56126 - Pisa/IT

Resources

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Abstract 1922P

Background

Thymic epithelial tumors (TETs) are rare neoplasms and the mutations driving their growth have been partially elucidated. We designed a targeted resequencing assay specific for TETs.

Methods

Reviewing the literature, we identified frequently mutated genes in TETs and designed a custom panel of 77 genes for targeted resequencing specific for thymic tumors. Between 2021 and 2024, we collected tumor samples during surgical resections. We sequenced tumor and blood DNA to identify somatic mutations. Libraries were prepared using DNA Prep with enrichment and sequencing was conducted using NextSeq 550 (Illumina).

Results

We enrolled 70 TETs: 3 A, 21 AB, 6 B1, 4 B1/B2, 11 B2, 11 B2/B3, 6 B3, 1 micronodular, 1 metaplastic thymoma and 6 thymic carcinomas. For tumors, the average coverage was 758 reads (SD± 179) and 97% (SD± 12%) of the target sequences was covered with at least 50 reads. There were 150 somatic mutations in 53 genes: 84 were missense mutations, 5 nonsense, 54 synonymous and 7 insertion/deletions. At least one somatic mutation was observed in 43 tumors and 20 patients harbor multiple mutations. A B2 thymoma had the higher number of mutations: 12 synonymous and 12 missense including a GTF2I mutation. GTF2I mutation was the most common being present in 29 tumors (41%). Somatic GTF2I mutations determined the substitution of a leucine with a histidine on position 404. The frequency of GTF2I mutation was 67% in A thymoma, 76% in AB, 17% in B1, 50% in B1/B2, 27% in B2, 9% in B2/B3. 17% in B3, 33% in thymic carcinomas and in 1 micronodular thymoma. A and AB thymomas had more GTF2I mutations (75%) than thymic carcinomas and B histotypes (29%, p<0.0001). GTF2I mutation was more common in stage I-II (52%), than III-IV tumors (21%, p= 0.0115). Four out of 5 HRAS mutations cooccurred with GTF2I in an A(K117T), AB(G13R), B2 (K117T) and 1 thymic carcinoma (A146T), only the L133H mutation of HRAS did not occur in a GTF2I mutant tumor.

Conclusions

TETs exhibit a low mutational burden. GTF2I mutation was the most prevalent, particularly in early stages and within histotypes exhibiting a more indolent behavior. Recent studies have demonstrated that transgenic mice expressing mutated GTF2I in the thymus develop thymomas, thus confirming its oncogenic potential.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of Pisa.

Funding

Tuscany Region Ail Pisa: Grant in memory of Dr. Guido Arzilla.

Disclosure

All authors have declared no conflicts of interest.

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