Novel technology for improved detection of clinically relevant chromosomal rearrangements in tumors

All cells in our body contain chromosomes, which carry our genetic material. When a change occurs in the organization of the chromosomes, this is called a chromosomal rearrangement. Such rearrangements can come in the form of a translocation, which means that part of a chromosome is transferred to another chromosome. Other examples of chromosomal rearrangements include deletions – part of the genetic material is absent – or duplications – part of the genetic material is doubled.

Clinical relevance

Some chromosomal rearrangements are clinically relevant: they can lead to genetic diseases or cancer. Lymphoma, cancer of the body’s lymphatic system, can originate from translocations or other chromosomal rearrangements. Detecting these clinically relevant genetic changes is important for proper diagnosis of lymphoma. Therefore, researchers from the group of Wouter de Laat, in collaboration with biotech company Cergentis and lymphoma experts of 5 Dutch hospitals, developed novel technology for improved detection of chromosomal rearrangements in lymphatic tumors.

Novel technology

The technology called FFPE-TLC allows the researchers to detect translocations and other chromosomal rearrangements in selected target genes with increased sensitivity and specificity. Additionally, they developed the PLIER algorithm, which automizes the detection of these changes in patients’ genetic material. Thereby, the researchers greatly improve lymphoma diagnostics.

Improved diagnostics

The study, published in Nature Communications, analyzes 149 tumor samples of patients with lymphoma and shows that FFPE-TLC has clear advantages over FISH – the currently most common used method for translocation detection. FFPE-TLC not only yields more information, it also shows a better sensitivity and higher resolution.

“The FFPE-TLC approach promises to improve lymphoma diagnostics and may also be relevant for the detection of chromosomal rearrangements in other types of cancer, such as sarcoma and lung- and prostate cancer. Our collaboration therefore brings the field a major step forward,” concludes Wouter de Laat, lead researcher on the project.

Publication

Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing. Amin Allahyar et al., Nature Communications (2021).