TY - JOUR
T1 - Identification of genetic alterations in extramammary Paget disease using whole exome analysis
AU - Kiniwa, Yukiko
AU - Yasuda, Jun
AU - Saito, Sakae
AU - Saito, Rumiko
AU - Motoike, Ikuko N.
AU - Danjoh, Inaho
AU - Kinoshita, Kengo
AU - Fuse, Nobuo
AU - Yamamoto, Masayuki
AU - Okuyama, Ryuhei
PY - 2019/4
Y1 - 2019/4
N2 - Background: Extramammary Paget disease (EMPD)is a rare cutaneous malignant neoplasm, and the genomic alterations underlying its pathogenesis are unknown. Objective: To identify tumor-specific genomic alterations in EMPD. Methods: Exome analysis was performed in specimens from three EMPD patients, and target amplicon sequencing was done for genes frequently mutated in other adenocarcinomas. Results: Exome analysis revealed recurrent somatic mutations in several genes, includingTP53, PIK3CA, and ERBB2. We identified additional candidate exons by searching the COSMIC database for exons that are frequently mutated in other adenocarcinomas. We obtained 19 exons in 12 genes as candidate exons, and performed target amplicon sequencing in samples obtained from EMPD patients. New somatic mutations in the TP53 gene were identified in six EMPD patients. Single nucleotide polymorphism analysis revealed multiple chromosomal alterations in three EMPD specimens, and two specimens exhibited amplification of chromosome 12p13 and losses of 3p21–24, 7q22 and 13q12–21. Conclusion: Our comprehensive genetic analysis identified novel genomic alterations, and will inform treatment options for EMPD.
AB - Background: Extramammary Paget disease (EMPD)is a rare cutaneous malignant neoplasm, and the genomic alterations underlying its pathogenesis are unknown. Objective: To identify tumor-specific genomic alterations in EMPD. Methods: Exome analysis was performed in specimens from three EMPD patients, and target amplicon sequencing was done for genes frequently mutated in other adenocarcinomas. Results: Exome analysis revealed recurrent somatic mutations in several genes, includingTP53, PIK3CA, and ERBB2. We identified additional candidate exons by searching the COSMIC database for exons that are frequently mutated in other adenocarcinomas. We obtained 19 exons in 12 genes as candidate exons, and performed target amplicon sequencing in samples obtained from EMPD patients. New somatic mutations in the TP53 gene were identified in six EMPD patients. Single nucleotide polymorphism analysis revealed multiple chromosomal alterations in three EMPD specimens, and two specimens exhibited amplification of chromosome 12p13 and losses of 3p21–24, 7q22 and 13q12–21. Conclusion: Our comprehensive genetic analysis identified novel genomic alterations, and will inform treatment options for EMPD.
KW - Chromosomal copy number alteration
KW - ERBB2
KW - Exome
KW - Extramammary Paget disease
KW - PIK3CA
KW - TP53
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UR - http://www.scopus.com/inward/citedby.url?scp=85064503731&partnerID=8YFLogxK
U2 - 10.1016/j.jdermsci.2019.03.006
DO - 10.1016/j.jdermsci.2019.03.006
M3 - Article
C2 - 31023612
AN - SCOPUS:85064503731
VL - 94
SP - 229
EP - 235
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 1
ER -