UCL Cancer Institute

Molecular Cytogenetics Group

Group Leader: Dr Elisabeth Nacheva

Molecular Cytogenetics is concerned with the identification of genetics anomalies associated with the diagnosis and progression haematological malignancies. We have developed and extended the use of fluorescent in-situ hybridisation (FISH), array comparative hybridisation (aCGH) and next generation sequencing (NGS) for diagnostics. We are currently collaborating with Dr Panos Kottaridis seeking correlations between mutation status and response to therapy and Dr Christos Prokakis mapping variations in copy number changes in the brain of patients with Parkinson’s disease.

Research Interest

Our early adoption of genomic array technology (aCGH) allows us to screen CML samples for genome aberrations leading to a greater understanding of the mechanisms of disease progression (Fig 1).


Fig 1   Array CGH profile of chromosome 9 shows increased copy number (amplification) of sequences from the 9q34.12 region in CML blast crisis.

While genome loss, frequently cryptic, is uniquely associated with the lymphoid blast transformation (e.g. IKZF1 and CDKN2A genes on chromosomes 7 and 9 respectively), gains of chromosome regions 8q21/24, 17q11/24 and 19p are frequently present in myeloid blast transformation of CML (Fig 2). Genetic variations such as these shed light on the processes underlying disease onset and development. Current investigations include a review of the genomic profile of early progenitor cells (CD34+) in chronic disease searching for tell tale signs associated with the development of more aggressive stages of CML. Another study explores the rare Ph(+) form of acute myeloid leukaemia (AML) for associations with other BCR/ABL1 positive diseases eg CML and Ph(+) acute lymphocytic leukaemia (ALL).

aCGH profile

Fig 2   A CGH profile of chromosomes 7 & 9 showing loss of copy number (deletion). Smoothed data from very high (~ &250bp ) resolution aCGH (blue) confirms the low resolution results (red) in agreement with FISH mapping.

As a pioneer in the use of FISH for research and diagnostics, I have a longstanding interest in the development of new fluorescent probes for the detection of fusion genes, amplifications and deletions. This has led us to the identification of the chromosome telomere region as site for genomic integration of the HHV6 virus(Fig 3) and to our current programme for screening bone marrow donors treated with GCSF for possible genomic changes.

HHV6 virus

Fig 3   HHV6 virus incorporation


Group Members

•  A Chanalaris - Post doc
•  M Valganob - Research assoc
•  A Virgilli - PhD student
•  D Brazma MD Research assoc
•  J Howard-Reeves - Research assoc