NGS analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors
Session type: Poster / e-Poster / Silent Theatre session
So far, there are very few reports about subsequent extrapancreatic malignant neoplasms (SMNs) developed among pancreatic ductal adenocarcinoma (PDAC) long-surviving patients. In addition, their genetic background has never been described previously. This is the first study describing genetic background of PDAC long-term survivors with SMNs in Central Europe.
CZECANCA, custom designed panel encompassing 219 selected genes was used for the germline targeted NGS analysis of cancer-predisposition and candidate genes of 118 PDAC patients, who underwent curative-intent surgery between the years 2006 and 2011 in The University Hospital, Olomouc. Acquired NGS data were processed following in-house bioinformatics pipeline based on standard tools.
Targeted next-generation sequencing has identified missense germline variant in PTCH1 in a patient with malignant melanoma and a rare RECQL5 variant in a patient with prostate cancer, both with in silico predicted deleterious effect. No splicing or truncating variants have been observed.
Although pathogenic variants in RECQL5 gene have been predicted, their biochemical or clinical consequences could not be verified due to the lack of individuals carrying loss of function variant in homozygous form. Potential embryonic lethality of such condition has been suggested, but no information about pathological role of haploinsufficiency was reported so far.
Low PTCH1 expression was recently demonstrated as independent predictive marker for failure of imatinib therapy in patients with chronic myeloid leukemia, therefore, besides the potential diagnostic role, predictive therapeutic potential of deleterious variants must also be considered.
Our study unveiled two potential candidate genes which might rather modify than cause PDAC as well as subsequent secondary tumors and must be verified by further studies, even with regard to their functional impact.
This work was supported by the Ministry of Health of the Czech Republic grant no. 16-28375A.