480MO - Prevalence and characteristics of TP53 Y220C mutations in patients with solid malignancies

Background

Somatic TP53 mutations are found in nearly all cancer types. promising small molecules targeting y220c hotspot mutation are under investigation in phase I clinical trials. We determined the prevalence and characteristics of TP53 Y220C mutations among different solid malignancies.

Methods

Patients with TP53 Y220C mutations were identified. Clinical data, tumor details, and genomic data were analyzed from the AACR Project GENIE registry cohort v15.1 public.

Results

Among 197,980 samples from 171,957 patients, we identified <1% (n=1,205 samples from 1,116 patients) positive for TP53 Y220C mutations. Cancer types among those 1,205 samples, were mainly ovarian cancer (17.2%), NSCLC (13%), breast cancer (9.4%), colorectal cancer (9 %), pancreatic cancer (8.3%), glioma (6.4%), cancer of unknown primary (4.6 %). Regarding the TP53 Y220C mutant ovarian cancer (n=200 patients), the median age at sequencing was 64 years, 81.6% were high-grade serous histology, 6.3% and 6.8% were co-mutants for BRCA1, and BRCA2 respectively. Furthermore, for NSCLC patients with TP53 Y220C mutations (n=144 ), the median age at sequencing was 67 years, 52.8% were females, 57.3% were adenocarcinoma, 26.1% were squamous histology, 28.0%, 14.0% and 5.8% were co-mutant for EGFR, KRAS and ALK respectively. Also, in patients with breast cancer (n=108), the median age at sequencing was 55 years, 54.9% were invasive ductal carcinoma, and 100% were co-mutant for COL2A1. Additionally, for colorectal cancers (n=107), the median age at sequencing was 59 years, 53.3% were males, 39.4% and 12.8% were co-mutants for KRAS and BRAF respectively. Also, for pancreatic cancers (n=98), the median age at sequencing was 66 years, 56.1% were females, and 94.0% were co-mutants for KRAS. Of the 69 glioma patients, the median age at sequencing was 44 years, 62.3% were males, 23.4% were glioblastoma, 59.7% and 40.6% were co-mutants for IDH1 and ATRX respectively. Of 55 patients with CUP, the median age at sequencing was 67 years. 56.4% were females, and 27.3% were co-mutants for KRAS.

Conclusions

TP53 Y220C mutations are widely distributed among solid malignancies. the prevalent co-mutations with it could be of prognostic value and help stratify patients in the ongoing clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.