HYSP53
Research type
Research Study
Full title
The Role of Hypoxia as a Selective Pressure for TP53 Mutations
IRAS ID
229924
Contact name
Nandita deSouza
Contact email
Sponsor organisation
The Institute of Cancer Research
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary:
Cancer tissue harbours a multitude of genetic alterations, and it is well-established that when certain key alterations develop, they are powerful determinants of tumour behaviour (growth rate, potential to spread). One of the most sinister and well-recognized alterations is in a gene called TP53. Another feature of tumours that results in resistance to treatment and poor outcome is a low oxygen level within tumour tissue. However, whether alterations in TP53 are driven by low oxygen levels is not established.Endometrial cancer is a good model to study the relationship between low tumour oxygen levels and alterations in TP53 within tumour. Firstly, it is a common gynaecological malignancy, (9,300 new cases annually in the UK) with two recognized types based on the appearance and behaviour of the tumour. In type I (endometrioid and mucinous carcinomas), alterations in TP53 are uncommon (15%), while in type II (serous and clear cell carcinomas) they are common (88%). In-line with this, the survival of patients with Type 2 cancer is worse. Secondly, endometrial cancer is routinely assessed at diagnosis using Magnetic Resonance Imaging. This non-invasive scanning technique can be manipulated to derive additional information about the oxygen status of the whole tumour and regions within it. Finally, the primary management of endometrial cancer is surgical and involves hysterectomy. This makes it is possible to obtain fresh tumour tissue at the time of surgery from regions that have been identified on imaging as having low vs. high levels of oxygen and to establish their TP53 status. In this study, therefore, we will establish the regional oxygen distribution within endometrial cancers at diagnosis, and relate them to the alterations in TP53 from fresh tissue samples from selected regions using gene sequencing. Understanding how highly deleterious mutations arise in cancer might provide new avenues for intervention and control.
Lay summary of study results: No results for this study due to very low numbers of eligible patients being surgically treated at the Royal Marsden Hospital and failure to recruit them.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
17/YH/0371
Date of REC Opinion
8 Dec 2017
REC opinion
Further Information Favourable Opinion