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2014 MRC성과발표회
Abstract Information
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< Abstract Sample >
Progression of naive intraepithelial neoplasia genome to
aggressive squamous cell carcinoma genome of uterine cervix
Youn Jin Choi2, , Seung-Hyun Jung1 ,3, Min Sung Kim2, In-Pyo Baek1, 3, Sung Hak Lee4, Ah
Won Lee4, Soo Young Hur5, Tae-Min Kim6, Yeun-Jun Chung1, 3 and Sug Hyung Lee2
Departments of 1Microbiology, 2 Pathology,3 Integrated Research Center for Genome
Polymorphism, 4 Hospital Pathology, 5 Obstetrics/Gynecology and 6 Medical Informatics,
College of Medicine, The Catholic University of Korea
Cervical intraepithelial neoplasia (CIN) progresses to cervical squamous cell carcinoma
(CSCC) with a latency. To define genomic landscapes of CIN as well as progression
mechanism of CIN to CSCC, we performed whole-exome sequencing and copy number
profiling of three CINs, a microinvasive carcinoma (MIC) and four CSCCs. Mutation
numbers of the CINs were significantly fewer than those of the MIC/CSCCs (median of 49
versus 90, respectively; P = 0.036). Also, number of driver mutations in the CIN (one
mutation) was significantly fewer than that of the CSCC/MICs (24 mutations, including
TP53, PIK3CA and STK11) (P = 0.018). Importantly, PIK3CA was altered in all MIC/CSCCs
by either mutation or amplification. Moreover, the CINs did not harbor any driver
mutations identified in CSCC by the previous study. The CINs harbored significantly lower
numbers of copy number alterations (CNAs) than the MIC/CSCCs (median of 4 versus 18
CNAs, respectively; P = 0.036). Pathway analysis of the mutations predicted that the
MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR
signaling pathway and cell migration that were depleted in the CINs. The mutation-based
estimation of evolutionary ages identified that CIN genomes were younger than
MIC/CSCC genomes. The data indicate that CIN genomes harbor HPV infection and
unfixed non-driver mutations but require additional driver hits such as PIK3CA, TP53,
STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain
the long latency from CIN to CSCC progression and provide useful information for
molecular diagnosis of CIN and CSCC.
References
[1] zur Hausen H. Papilloma viruses and cancer: from basic studies to clinical application.
Nat Rev Cancer 2002;2: 342-350.
[2] Woodman CB, Collins SI, Young LS. The natural history of cervical HPV infection:
unresolved issues. Nat Rev Cancer 2007;7: 11-22.
[3] Martin CM, O'Leary JJ.Histology of cervical intraepithelial neoplasia and the role of
biomarkers. Best Pract Res Clin Obstet Gynaecol 2011;25: 605-615.
Keywords
Uterine cervix cancer, Cervical intraepithelial neoplasia, Cervical squamous cell carcinoma,
Mutations, Copy number alterations, Cancer progression
2014
MRC 성과발표회
Name : Youn Jin Choi
Pi
Affiliation : The Catholic Univeristy of Korea
Position : Student
E-mail : [email protected]
Field of Expertise : Obstetrics & Gynecology
cture
Education :
2009- 2012
Master’s Degree in Medical Science
Department of Obstetrics and Gynecology,
University of Korea, Seoul
the Catholic
2001- 2007
Graduate of Bachelor’s degree in Medical Science, the Catholic
University of Korea, Seoul
2013- Present
Course of physician scientist program, the Catholic University of
Korea, Seoul
Professional Experience : (less than 5 experiences)
2007- 2008
Intern training
: Kangnam St. Mary's Hospital, Seoul &
St. Vincent’s Hospital, Suwon;
The Catholic University of Korea, Seoul
2008-2012
Residency training
Department of Obstetrics and Gynecology
: Kangnam St. Mary's Hospital, Seoul &
St. Vincent’s Hospital, Suwon &
Bucheon St. Mary’s Hospital, Bucheon &
Incheon St. Mary’s Hospital, Incheon &
Seoul St. Mary’s Hospital, Seoul;
The Catholic University of Korea, Seoul
s
2012-2013
Fellow
Department of Obstetrics and Gynecology
: Seoul St. Mary’s Hospital, Seoul;
The Catholic University of Korea, Seoul
Selected Publications : (less than 5 papers)
1.
Choi YJ1, Oh HR1, Choi MR1, Gwak M1, An CH2, Chung YJ3, Yoo NJ1, Lee SH4. Frameshift
mutation of a histone methylation-related gene SETD1B and its regional heterogeneity in
gastric and colorectal cancers with high microsatellite instability. Hum Pathol. 2014
Aug;45(8):1674-81
2.
Choi YJ1, Kim MS, An CH, Yoo NJ, Lee SH. Regional bias of intratumoral genetic
heterogeneity of nucleotide repeats in colon cancers with microsatellite instability. Pathol
Oncol Res. 2014 Oct;20(4):965-71
3.
Choi YJ1, Yoo NJ, Lee SH. Choi YJ1, Yoo NJ, Lee SH. Down-regulation of ROBO2 Expression
in Prostate Cancers. Pathol Oncol Res.2014 Jul;20(3):517-9.