Table 1.

Discrepancies in genetic alteration between primary tumor and model system. Clonal evolution occurs due to accumulation of genetic alterations while model system is constructed from primary tumor. Clonal evolution leads to discrepancies in genetic alteration profiles between primary tumor and model system. This table summarizes the differences in genetic alterations between the two groups.

Genetic alteration	Primary tumor	Model system	Reference
SV
SV events concordance	•The frequency and pattern of SV events were sufficiently different among PDAC tumors to allow classification into four subtypes according to the information: stable, unstable, locally rearranged, and scattered. •Stable subtype was characterized by 50 or fewer SV events whereas unstable subtype had over 200. •Locally rearranged subtype accounts for 30 % of the total sample and had critical focal events on a small number of chromosomes. •Scattered subtype showed the largest proportion (36 %) with less than 200 SV events.	•SV event concordance was higher between PDX and organoid than between primary tumor and model systems. •The comparison of PDAC PDX and matched primary tumor showed low SV event concordance in 60 % of samples. •Organoid had a similar SV event pattern to PDX.	[14], [52]
Insertion and deletion	•Total of 11,868 SV events were identified in 100 PDAC primary tumors. •Intra-chromosomal events were relatively abundant, with the highest proportion of rearrangements (5,860) and the lowest proportion of duplications (1 2 8). •The number of deletions was 1,393.	•PDAC PDX had more than twice the indels as matched primary tumor, suggesting the accumulation of genetic alterations in the DNA repair pathway of the PDX.	[14], [52]
Mutation
Significantly mutated genes	•As PDAC progressed through the PanIN stages, mutations accumulated in KRAS, CDKN2A, TP53, and SMAD4 genes in order. •A large-scale PDAC mutation showed that mutations in KRAS (93 %), TP53 (72 %), SMAD4 (32 %), and CDKN2A (30 %) were found most frequently in the cohorts.	•Mutations in KRAS, TP53, and CDKN2A genes found in primary tumors were conserved in matched model systems. •However, the VAF of mutations was higher than the primary tumor in the model system (VAF median: primary tumor = 12.44 and model system = 57.69).	[34], [50], [53], [54]
KRAS mutation genotype	•Based on genomic profiles of the tumors from 150 pancreatic cancer patients, KRAS G12D, G12V, and G12R mutations accounted for approximately 44 %, 29 %, and 20 %, respectively.	•In early passage, the KRAS MAFs of early organoids were 33 %, 9 %, and 1 % for G12V, G12D, and G12R, respectively. •In passage 3, the MAF of KRAS G12R dominated with 51 %, and KRAS G12V and G12D mutation disappeared.	[35], [54]
CNV
Loci and concordance	•More than one-third of PDAC tumors had significant CNV. •In PDAC tissues, the copy number of GATA6, ERBB2, KRAS, AKT2, and MYC were amplified, whereas the copy number of CDKN2A, SMAD4, ARID1A, and PTEN were deleted.	•In the genome-wide view of CNV, the concordance was high between primary tumor and PDX. •At the local chromosome levels, the CNV of primary tumor and PDX was distinct.	[14], [54], [55]
Recurrence	•61 arm-level recurrent CNVs were identified from TCGA data.	•As the PDX was established and passaged, the recurrent CNVs disappeared in PDX.	[15]
Copy number of CDKN2A	CNV mean log2 ratio was approximately −1.5 for CDKN2A and CDKN2B.	•In the organoid, CNV mean log2 ratio was remarkably decreased by approximately −6 for CDKN2A and CDKN2B.	[56]