Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
- Klíčová slova
- PIK3CA, MTOR, TSC1, TSC2, low-grade oncocytic tumour, oncocytoma,
- MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- karcinom z renálních buněk * genetika MeSH
- ledviny MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mutace MeSH
- nádory ledvin * genetika MeSH
- oxyfilní adenom * genetika MeSH
- TOR serin-threoninkinasy genetika MeSH
- transkripční faktor GATA3 genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy třídy I MeSH
- GATA3 protein, human MeSH Prohlížeč
- MTOR protein, human MeSH Prohlížeč
- PIK3CA protein, human MeSH Prohlížeč
- TOR serin-threoninkinasy MeSH
- transkripční faktor GATA3 MeSH
The level of expression of transcription factor genes (GATA-3, TBX21, IL23A), and changing of oxidative modification of proteins in young and elderly healthy persons was studied. The results of evaluation of gene expression, GATA-3 in lymphocytes showed the increased expression of GATA-3 in elderly people in comparison with the young. Women demonstrated higher expression of GATA-3 in compare with men. Study of IL-2p showed reduced levels of expression in aged humans compared to young. TVH21 expression level showed a reduction expression in both men and women. Comparative analysis of protein oxidation in blood plasma of young and elderly people showed an increase in the intensity of oxidative modification of proteins in the elderly.
Проведено исследование уровня экспрессии генов транскрипционных факторов (GATA-3, TBX21, IL23A), а также изменения окислительной модификации белков у молодых, и пожилых здоровых людей. Результаты оценки экспрессии генов, GATA-3 в лимфоцитах показал, что у пожилых людей наблюдается увеличение экспрессии GATA-3 по сравнению с молодыми. При сравнении показателей экспрессии у мужчин и женщин обнаружено, что у женщин экспрессия GATA-3 выше, чем у мужчин. Исследование гена IL23A обнаружило снижение уровня экспрессии у пожилых людей по сравнению с молодыми. Уровень экспрессии ТВХ21 показал также уменьшение экспрессии как у мужчин, так и у женщин. Сравнительный анализ окисления белков в плазме крови у молодых и пожилых людей выявил повышение интенсивности окислительной модификации белков у пожилых людей.
- Klíčová slova
- aging, oxidative modification of protein, transcription factors,
- MeSH
- dospělí MeSH
- interleukin-23 - podjednotka p19 genetika MeSH
- lidé MeSH
- proteiny T-boxu genetika MeSH
- senioři MeSH
- sexuální faktory MeSH
- stanovení celkové genové exprese MeSH
- stárnutí * genetika imunologie MeSH
- transkripční faktor GATA3 genetika MeSH
- transkripční faktor T-bet MeSH
- transkripční faktory TCF genetika metabolismus MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- GATA3 protein, human MeSH Prohlížeč
- IL23A protein, human MeSH Prohlížeč
- interleukin-23 - podjednotka p19 MeSH
- proteiny T-boxu MeSH
- transkripční faktor GATA3 MeSH
- transkripční faktor T-bet MeSH
- transkripční faktory TCF MeSH
