목차

I. Introduction 1
II. Materials and Methods 12
A. Sample collection from patients 12
B. Establishment of PDX model 12
C. Whole exome sequencing 13
D. RNA sequencing 13
E. Separation of human-derived reads from PDX raw data 14
F. Somatic variant calling analysis 14
G. Copy number variation analysis 15
H. Clonal evolution analysis 16
I. Evaluation of tumor cellularity 16
J . Gene expression profiling 17
K. Subtyping for primary tumor and PDX using published gene signatures 17
L. Gene signature extraction and subtyping for novel PDX subtypes 18
M. Definition of nomenclature for novel PDX subtypes 19
N. Deconvolution analysis using published single cell RNA-seq data 20
O. Confirmation of subtype transition in primary tumor and PDX 21
III. Results 22
A. Patients cohort information 22
B. NGS samples configuration 25
C. Comparison of mutation profiling between primary tumor and PDX 29
D. CNV analysis to identify the discrepancy between primary tumor and PDX 33
E. Estimation of tumor cellularity for primary tumor and PDX 38
F. Clonal evolution from primary tumor to PDX 41
G. Subtyping for primary tumor using Bailey subtype 44
H. Definition of novel PDAC PDX subtype 51
I. Transition of PDAC primary tumor subtype during PDX establishment 71
V. Discussion 74
V. References 79
VII. 국문요약 87