Researchers from the group of Wouter de Laat (UMC Utrecht and Hubrecht Institute), in collaboration with biotech company Cergentis and lymphoma experts of 5 Dutch hospitals, developed a novel technology for improved detection of clinically relevant chromosomal rearrangements in tumors. The method, named FFPE-TLC technology, promises to improve diagnostics for lymphoma and may also be relevant for rearrangement detection in other cancers such as sarcoma and lung- and prostate cancer. The study was published in Nature Communications on June 7.

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 – when 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 prof. dr. Wouter de Laat, in collaboration with biotech company Cergentis and lymphoma experts of 5 Dutch hospitals, developed a novel technology for improved detection of chromosomal rearrangements in lymphatic tumors.

Novel technology
The technology, named formalin-fixed, paraffin-embedded targeted locus capture (FFPE-TLC), allows researchers and pathologists to detect translocations and other chromosomal rearrangements in selected target genes with increased sensitivity and specificity. Additionally, they developed the PLIER algorithm, which automates the detection of these changes in patients’ genetic material. Thereby, the researchers greatly improved lymphoma diagnosis.

Improved diagnostics
The study, published in Nature Communications, analyzed 149 tumor samples of patients with lymphoma and shows that FFPE-TLC has clear advantages over fluorescence in situ hybridization (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 diagnosis 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, principal investigator on the project.

Publication
Allahyar A, Pieterse M, Swennenhuis J, Los-de Vries GT, Yilmaz M, Leguit R, Meijers RWJ, van der Geize R, Vermaat J, Cleven A, van Wezel T, Diepstra A, van Kempen LC, Hijmering NJ, Stathi P, Sharma M , Melquiond ASJ , de Vree PJP , Verstegen MJAM , Krijger PHL , Hajo K, Simonis M, Rakszewska A, van Min M, de Jong D, Ylstra B, Feitsma H, Splinter E, de Laat W. Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing. Nature Communications 2021;12:3361