Circulating nucleic acids for detection and monitoring of cancer
Research in my group is focused on circulating nucleic acids for early detection and monitoring of breast cancer. In collaboration with Prof RC Coombes at Imperial College, I lead an integrated programme of clinical and translational research between the two universities funded by a Cancer Research UK.
We were the first to describe molecular portraits of circulating cell-free DNA (cfDNA) using Affymetrix® SNP 6.0 Arrays and our work was published in the top-ranked journal Genome Research. The paper was recommended by Faculty 1000 (F1000) as “an example of bench to bedside science that might be useful in the risk assessment and the monitoring of cancer”.
We were able to distinguish between patients with breast cancer and healthy female controls by comparison of cfDNA profiles and we demonstrated for the first time that tumour specific changes are detectable in cfDNA a decade after treatment and during clinical remission, suggesting the patient has a persistent but dormant disease. Importantly this indicates that the dormant phase of breast cancer has a genomic signature, which could be used to develop blood monitoring tests.
Our recent work has highlighted the importance of CNV as well as somatic mutations in cfDNA for monitoring tumour evolution and emergence of resistance to endocrine therapy as well as the need to consider both cfDNA and circulating tumour cells (CTCs) in clinical decision making in metastatic breast cancer.
My lab is also the cfDNA 'hub' for the TRACERx national lung cancer trial. I also lead the cfDNA advisory group for the 100,000 Genomes project led by Genomics England and serve on a number of advisory boards and editorial boards of international scientific journals.
To support our research we implemented Good Clinical Laboratory Practice within my research group; compliance with this QA system is essential for a laboratory engaged in translational research studies relating to clinical trials.
Shaw JA, Graham TA, Stebbing J. Genomic instability in pre-neoplastic colonic lesions. Oncogene. 2013 Feb 11. doi: 10.1038/onc.2013.21.
Coombes RC, Tat T, Miller ML, Reise JA, Mansi JL, Hadjiminas DJ, Shousha S, Elsheikh SE, Lam EW, Horimoto Y, El-Bahrawy M, Aboagye EO, Contractor KB, Shaw JA, Walker RA, Marconell MH, Palmieri C, Stebbing J. An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study). Ann Oncol. 2012 Dec 11.
Guttery DS, Blighe K, Page K, Marchese SD, Hills A, Coombes RC, Stebbing J, Shaw JA. Hide and seek: tell-tale signs of breast cancer lurking in the blood. Cancer Metastasis Rev. 2012 Oct 30.
Stebbing J, Filipovic A, Lit LC, Blighe K, Grothey A, Xu Y, Miki Y, Chow LW, Coombes RC, Sasano H, Shaw JA, Giamas G. LMTK3 is implicated in endocrine resistance via multiple signaling pathways. Oncogene. 2012 Aug 6.
Whale AS, Huggett JF, Cowen S, Speirs V, Shaw J, Ellison S, Foy CA, Scott DJ. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res. 2012; 40(11):e82.
Shaw JA, Page K, Blighe K, Hava N, Guttery D, Ward B, Brown J, Ruangpratheep C, Stebbing J, Payne R, Palmieri C, Cleator S, Walker RA and Coombes RC. Genomic analysis of circulating cell free DNA infers breast cancer dormancy. Genome Res. 2012 Feb;22(2):220-3. Recommended by F1000: Karnani N, Dutta A: 2012. F1000.com/13923982#eval15395063.
Payne RE, Hava NL, Page K, Blighe K, Ward B, Slade M, Brown J, Guttery DS, Zaidi SA, Stebbing J, Jacob J, Yagüe E, Shaw JA, Coombes RC. The presence of disseminated tumour cells in the bone marrow is inversely related to circulating free DNA in plasma in breast cancer dormancy. Br J Cancer. 2012 Jan 17;106(2):375-82.
Page K, Hava N, Ward B, Brown J, Guttery DS, Ruangpratheep C, Blighe K, Sharma A, Walker RA, Coombes RC, Shaw JA. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer. 2011; 104(8):1342-8.
Shaw JA, Brown J, Coombes RC, Jacob J, Payne R, Lee B, Page K, Hava N, Stebbing J. Circulating tumor cells and plasma DNA analysis in patients with indeterminate early or metastatic breast cancer. Biomark Med. 2011; 5(1):87-91.
Guttery DS, Hancox RA, Mulligan KT, Hughes S, Lambe SM, Pringle JH, Walker RA, Jones JL, Shaw JA. Association of invasion-promoting tenascin-C additional domains with breast cancers in young women. Breast Cancer Res. 2010;12(4):R57