Comprehensive Approach to Genomic and Immune Profiling: Insights of a Real-World Experience in Gynecological Tumors

Abstract

Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.

Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center

“…Of these patients, a total of 26 (0.84) underwent successful genetic testing, which ultimately resulted in an MTB statement. The overall size of this cohort (n = 31) is in accordance with analyses published by other cancer centers, e.g., the Medical University of Vienna, Austria [31], the Hospital Universitario Fundación Jiménez Díaz [32] or the University of Oklahoma Health Sciences Center, USA [29].…”