Uspešno genetsko testiranje 59 let starega vzorca tkiva Successful genetic testing of a 59-year-old tissue sample

the significance of archival samples in determining hereditary cancer predisposition

Abstract

Predstavljamo uspešno genetsko analizo 59 let starega, arhivskega, v formalinu fiksiranega in v parafin vklopljenega (FFPE) vzorca tkiva z namenom opredelitve dedne predispozicije za razvoj raka. V družinah z obremenilno družinsko anamnezo raka, kjer ključni oboleli sorodniki niso več živi, je povednost standardnega genetskega testiranja živih družinskih članov pogosto omejena. V predstavljenem primeru je bila iz tumorskega vzorca, odvzetega leta 1960, izolirana DNA in izvedeno sekvenciranje naslednje generacije (NGS). Kljub starosti vzorca so bili doseženi vsi parametri kakovosti za zanesljivo molekularno-genetsko analizo. Ugotovljena je bila patogena različica CHEK2:c.1100del p.(Thr367Metfs*15), povezana s povečano ogroženostjo za razvoj raka dojk. Družinsko testiranje je omogočilo natančnejšo opredelitev ogroženosti pri živih sorodnikih in ustreznejše preventivne usmeritve. Opisani primer poudarja klinično vrednost analize arhivskih FFPE vzorcev pri genetski obravnavi družin s sumom na dedno nagnjenost k raku ter odpira vprašanje pomena dolgoročne hrambe reprezentativnega histološkega materiala za diagnostične, preventivne in raziskovalne namene.

Abstract (Eng)

We present a successful genetic analysis of a 59-year-old archival formalin-fixed, paraffin-embedded (FFPE) tissue sample for the assessment of hereditary cancer predisposition. In families with a strong history of cancer where key affected relatives are deceased, standard germline testing in living family members may prove uninformative. Archival tumor material may therefore represent an important source of genetic information. In the case presented here, DNA was extracted from a tumor sample collected in 1960 and analyzed using next-generation sequencing (NGS). Despite the advanced age of the specimen, all quality criteria required for reliable molecular genetic analysis were met. A pathogenic variant, CHEK2:c.1100del p.(Thr367Metfs*15), associated with an increased risk of breast cancer, was identified. Subsequent cascade testing enabled a more accurate assessment of cancer risk among living relatives and appropriate preventive recommendations. This case demonstrates the clinical utility of archival FFPE tissue samples in the genetic evaluation of families with suspected hereditary cancer predisposition. It also highlights the importance of long-term preservation of representative histological material for diagnostic, preventive, and research purposes.