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MYB rearrangements in Adenoid Cystic Carcinoma: protagonists or secondary characters?

Descrizione del progetto

Il ruolo dei riarrangiamenti del gene MYB nel cancro

Il carcinoma adenoido-cistico (AdCC) è un cancro raro con un comportamento clinico diversificato in base al sito del tumore primario. L’AdCC ospita i riarrangiamenti della famiglia di geni MYB dei fattori di trascrizione derivati dalle traslocazioni cromosomiche. Lo scopo del progetto SALMYB, finanziato dall’UE, è quello di individuare le cellule che trasportano i riarrangiamenti MYB, chiarirne le funzioni e sviluppare terapie mirate ai MYB. Gli scienziati, avvalendosi di metodi all’avanguardia in biologia molecolare e cellulare oltre che dell’ingegneria genetica e tessutale, decifreranno l’impatto dei riarrangiamenti MYB su morfologia, differenziazione, proliferazione, migrazione e invasione cellulari. I risultati del progetto si estenderanno ad altre neoplasie contenenti le aberrazioni MYB.

Obiettivo

Adenoid cystic carcinoma (ACC) is both a rare disease (limited scientific data and professional expertise) and a cancer (complex tumour biology and evasion of conventional therapies). Clinical behaviour differs depending on primary tumour site; salivary gland ACC has poorer prognosis than breast ACC. A majority of ACC harbour MYB rearrangements resulting from chromosomal translocations, with the fusion of MYB and NFIB or MYBL1 and NFIB being the most frequent. The role of translocations in tumourigenesis and whether cells from different primary sites respond differently has not been determined. Identification of specific cell types carrying the translocation and location within the tumour microenvironment might enable development of MYB target-therapies. Our main objective is to elucidate the function of MYB rearrangements in normal salivary and mammary gland cells and the expression of the novel fusion genes in salivary gland and breast ACC. Normal human cells will be transfected with MYB-NFIB and MYBL1-NFIB fusion transcripts and fusion negative, fusion positive and combinations of cells will be compared in terms of cell morphology, differentiation, proliferation, migration and invasion. 3D models, more closely mimicking an in vivo tumour, will be compared to monolayer cultures. In situ localisation of MYB-NFIB and MYBL1-NFIB in salivary gland and breast ACC will be assessed using a novel technology, BaseScope. This ambitious research project will determine the consequences of MYB rearrangements using state-of-the-art methods in molecular and cellular biology, genetic and tissue engineering and pathological anatomy. The project has clear translational potential with social, cultural and economic impacts. Transfer of results to other cancers harbouring MYB rearrangements (eg leukaemia, colon cancer) and our methods in assessing other tumours characterised by chromosomal translocations, eg prostate, colorectal and non-small-cell lung cancer, are further outcomes.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-MSCA-IF-2019

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Coordinatore

THE UNIVERSITY OF SHEFFIELD
Contributo netto dell'UE
€ 212 933,76
Indirizzo
FIRTH COURT WESTERN BANK
S10 2TN SHEFFIELD
Regno Unito
Regione
Yorkshire and the Humber South Yorkshire Sheffield
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 212 933,76