Abstract 480P
Background
Colorectal cancer (CRC) is one of the most prevalent solid cancers, and its incidence is increasing in young patients worldwide. So far, knowledge of adolescents and young adults (AYAs) with CRC has been still limited. In this study, we aimed to elucidate the unique genomic and clinical characteristics in AYAs with CRC.
Methods
A total of 81 Chinese AYAs (<= 35 years old) with CRC were enrolled in this study. Targeted deep sequencing with 450 cancer-associated genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumour samples and matched blood samples. Comprehensive genomic profiling was performed; this included analysis of single nucleotide variants (SNV), short and long insertions and deletions (Indel), and copy number variations (CNV). Gene fusions were analysed by OrigiFus, an in-house developed method.
Results
Our study showed that 98.8% (80/81) of AYAs harboured at least one genomic alteration. The median tumour mutational burden (TMB) was 5.4 muts/Mb (ranged from 0.6-525.6 muts/Mb) and the median age was 31 yrs (ranged from 17-35 yrs). Among the total 81 AYAs, 60 (74.1%) had advanced CRC (stage > II) and 14 (17.3%) showed microsatellite instability (MSI-H). The most frequent alterations were detected in TP53 (72.8%), KRAS (45.7%), SMAD4 (39.5%), APC (39.5%) and PIK3CA (32.1%). Alterations of APC were decreased compared to previous studies (39.5% vs 71%) (Liang Huang et al., Journal of Clinical Oncology 2020 38:4_suppl, 222-222) while an opposite trend was found in SMAD4 (39.5% vs 22%) and PIK3CA (32.1% vs 21%). Alterations of TP53 (84.1% vs 28.6%, P < 0.001) and SMAD4 (47.6% vs 14.3%, P = 0.03) were significantly higher in the microsatellite stable (MSS) group compared to MSI-H group. In contrast, alterations of APC (85.7% vs 28.6%, P < 0.001) and PIK3CA (78.6% vs 22.2%, P < 0.001) were significantly higher in the MSI-H group compared to the MSS group. Alterations in PIK3CA were identified more frequently in early stage CRC(stage <= II) compared to advanced stages (57.1% vs 25%, P = 0.04).
Conclusions
Our study revealed that AYAs with CRC had distinct genomic features with high levels of SMAD4 and PIK3CA alterations and lower levels of APC alterations, which is different to what is observed in adult CRC patients. Further in-depth analyses of the genomic landscape of AYAs with CRC are needed to reveal distinct therapeutic avenues.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumour Hospital.
Funding
Has not received any funding.
Disclosure
S. Yuan, K. Wang, L. Zhang, H. Chen: Full/Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.