Abstract 572P
Background
Colorectal cancer (CRC) is a heterogeneous disease with multiple subtypes that differ in their clinical and molecular features. The presence of neoantigens derived from somatic mutations is a promising avenue for immunotherapy in CRC. However, the heterogeneity of the neoantigen landscape among CRC subtypes remains unclear.
Methods
We analyzed the whole-genomes and transcriptomes of 1063 CRC patients from a Swedish large cohort. HLA alleles were called by at least two HLA callers including HLA-HD, HLA-LA, Kourami, OptiType, PHLAT, Polysolver, xHLA for each patient. Neoantigens were predicted by pVACseq pipeline using the default settings.
Results
In total, 83,630 MHC class I neoantigens derived from 29,106 mutations (511,159 mutations were inputted) were predicted in 979 patients. Average 6.1 neoantigens were from 4,480 frameshift INDELs while only average 2.3 neoantigens were from 24,276 SNVs. Patients older than 80 years carried more neoantigens than those under 65 years, and women tended to have more neoantigens than men (Wilcoxon test, P<0.01). Tumor neoantigen burden was significantly higher in right-colon, stage II, and hypermutated (HM) tumors (P<0.0001). In total, 850 mutations were predicted to generate neoantigens in at least two patients, including KRAS G12D (6.3%), RNF43 G659X (6.1%), KRAS G12V (5.2%), TBC1D23 K647X (2.9%), and MSH3 K381X (2.8%). Neoantigen numbers from PODXL2 and CRAT mutations were significantly higher in consensus molecular subtype (CMS) 3 tumors, whereas neoantigens from JAG2 mutations were more common in CMS2 (chi-square test, P <0.05). Neoantigens derived from DNAH3, KRAS and ERBB2 mutations (37%, 47% and 52% respectively) in non-HM patients were significantly more than those (5%, 14% and 13% respectively) in HM patients. Furthermore, in stage I-III, nHM patients (n=11) with DNAH3 neoantigens have significantly longer overall survival than patients (n=24) with only DNAH3 mutations.
Conclusions
Our study constitutes the largest neoantigen dataset from integrated genome and transcriptome of CRC to date and illustrates the heterogeneity of the neoantigen landscape among CRC subtypes. The identified neoantigens may contribute to future individualized CRC immunotherapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Uppsala University; Umeå University; BGI-Shenzhen.
Funding
The Swedish Cancer Society; the Uppsala Cancer Foundation; the Guangdong Provincial Key Laboratory of Human Disease Genomics; the Swedish Government (CancerUU); the Erling-Persson Foundation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
538P - Single-center retrospective analysis of patients with brain metastases included in early phase clinical trials
Presenter: Giulia Pretelli
Session: Poster session 10
539P - Epidemiology and prognostic factors of lung cancer and brain metastases: A 10-year retrospective population cohort study in Girona, Spain
Presenter: Eduard Teixidor Vilà
Session: Poster session 10
540P - Impact of adjuvant radiotherapy (ART) on survival time in patients with hemangiopericytoma (HPC): A population study
Presenter: Tala Alshwayyat
Session: Poster session 10
541P - A multicenter study evaluating the clinical and molecular characteristics of adult patients with diffuse midline and non-midline K27M altered gliomas
Presenter: Manuel Mazariegos Rubi
Session: Poster session 10
542P - Drug screening in Li-Fraumeni syndrome brain tumor models
Presenter: Anna Kolodziejczak
Session: Poster session 10
543P - Bevacizumab and hydroxyurea treatment in grade 2 and 3 meningioma: A monocentric experience
Presenter: Giulia Cerretti
Session: Poster session 10
544P - Clinical and molecular features of primary central nervous system tumor with Lynch syndrome
Presenter: Nan Liu
Session: Poster session 10
545P - Antibody-fragment based immunotherapeutic approaches for medulloblastoma and rhabdomyosarcoma
Presenter: Judith Niesen
Session: Poster session 10
546P - Early urinary potassium level is predictive of delayed methotrexate (MTX) elimination in patients with primary central nervous system lymphoma (PCNSL)
Presenter: Alexandre Bertucci
Session: Poster session 10
547P - Clinicopathological and molecular study of embryonal tumours with multilayered rosettes
Presenter: Lianghong Teng
Session: Poster session 10