Abstract LB-268: Detection of TP53 clonal mutations in PAP test collected up to six years prior to high-grade serous epithelial ovarian cancer diagnosis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.LB-268-LB-268
• Main Authors: Pesenti, Chiara, Paracchini, Lara, Marchette, Martina Delle, Beltrame, Luca, Bianchi, Tommaso, Grassi, Tommaso, Buda, Alessandro, Landoni, Fabio, Ceppi, Lorenzo, Bosetti, Cristina, Paderno, Maria Chiara, Adorni, Marco, Vicini, Debora, Perego, Patrizia, Leone, Biagio Eugenio, Marchini, Sergio, Fruscio, Robert, D'Incalci, Maurizio
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2020-LB-268

Background: The low five-years survival rate of High Grade Serous Epithelial Ovarian Cancer (HGS-EOC) is mainly related to late diagnosis. The anticipation of diagnosis constitutes a crucial step to increase the curability of this disease. Aim: This study explores an innovative potential HGS-EOC screening approach exploiting PAP tests routinely executed for cervical cancer surveillance and the presence of TP53 clonal alterations in almost all HGS-EOCs. Indeed, it investigates the possibility to detect, in DNA purified from PAP tests collected by patients years before the diagnosis, the clonal pathogenic TP53 variant identified in the matched primary tumor biopsy. Study Design: This retrospective and longitudinal study was conducted on 17 advanced HGS-EOC patients. Next Generation Sequencing (NGS) was used to identify TP53 clonal mutations in tumor tissue. The presence of these TP53 variants was then assessed by the droplet digital PCR (ddPCR) in DNA purified from all available patients' PAP tests executed up to almost six years before diagnosis. Results: In each patient, one TP53 clonal somatic variant was identified by NGS in the primary tumor samples (Table 1). The presence of the TP53 variant was then investigated by ddPCR in matched Pap tests. In twelve out of 17 patients the TP53 variant was detectable in PAP tests collected within six months before diagnosis (T1) or earlier (T2, T3 and T4) (Table 1). For two patients (21561 and 21521) more PAP tests collected at different time before diagnosis (two/four and three/six years before diagnosis, respectively) were analyzed and the TP53 clonal variant was detected at all time points (Table 1). Table 1:NGS and ddPCR resultsPatient IDTP53 mutationNGS tumor mutated %PAP test (months before surgery)T1(0-6)T2(7-24)T3(25-48)T4(≥49)Time intervalddPCR mutated %Time intervalddPCR mutated %Time intervalddPCR mutated %Time intervalddPCR mutated %21561c.818G>A65.010.20.24--250.21490.2621585c.817C>T40.94--11.30.21---21567c.281C>A71.9830.07---21587c.469G>T15.122ND---21586c.818G>A79.73--19.30.15---21569c.574C>T62.365.21.18---21624c.820G>T86.72---37.50.0465.3ND21570c.844C>T89.190.32.62---21627c.425_427del76.040.72.4---21640c.993+2T>G70.68--8ND---21507c.1025G>C91.23--9.20.06---21635c.844C>T66.241.3ND---21549c. 393_395del54.06---31.2ND65.3ND21521c. 722 C>G61.15---26.70.0567.30.0721654c.586 C>T49.354.70.09---21665c. 393_395del45.34---37.6ND--21683c.602 T>A33.42--18.50.06---ND Not Detected Conclusion: This study demonstrates