Abstract 382P
Background
Cervical cancer is the second most common cancer among women in India, with 80% of cases diagnosed at advanced stages. Despite the standard treatment of concurrent pelvic radiotherapy and chemotherapy (CCRT), 30%-40% of patients experience treatment failure. The genomic factors contributing to CCRT resistance are not well understood. This study aims to uncover genomic alterations associated to CCRT responses in cervical cancer.
Methods
We collected 36 fresh tissue biopsies and 5 ml of blood from stage IIIB cervical cancer patients (19 responders and 17 non-responders). Genomic DNA was extracted and sequenced using the Novaseq 6000 platform, achieving 30x-50x coverage. The data was analyzed for single nucleotide variants, copy number alterations, and mutational signatures.
Results
Our study identified several highly mutated genes in cervical cancer, including EPPK1 (27%), MACF1 (27%), and KMT2D (27%), along with known significant genes like PIK3CA, FBXW7, KMT2C, ARID1A, and STK11. Mutation spectrum analysis showed a high C>T transition and C>G transversion rate, aligning with previous studies and a prevalent APOBEC mutagenesis pattern. Copy number alterations revealed amplifications in 7p, 9p, 11q, and 19p region, which include genes like EGFR, CD274, BRCA, and AKT2. Comparative analysis of genomic alterations between chemoradiation-resistant and sensitive patients revealed mutations in genes associated with DNA repair, and Wnt-beta catenin signaling pathways, exclusively in the non-responder group. Notably, complex genomic rearrangements were identified in 25% of non-responders, indicating a significant genomic instability in this group.
Conclusions
This study is an initial effort to map the genomic landscape of cervical cancer in India, revealing genetic factors linked to CCRT response, which may guide personalized and targeted therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.