Identification of genetic alterations in extramammary Paget disease using whole exome analysis

Yukiko Kiniwa; Jun Yasuda; Sakae Saito; Rumiko Saito; Ikuko N Motoike; Inaho Danjoh; Kengo Kinoshita; Nobuo Fuse; Masayuki Yamamoto; Ryuhei Okuyama

doi:10.1016/j.jdermsci.2019.03.006

Identification of genetic alterations in extramammary Paget disease using whole exome analysis

J Dermatol Sci. 2019 Apr;94(1):229-235. doi: 10.1016/j.jdermsci.2019.03.006. Epub 2019 Apr 11.

Authors

Affiliations

¹ Department of Dermatology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621 Japan.
² Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan; Miyagi Cancer Center, 47-1 Aza-nodayama, Medeshima-shiote, Natori, Miyagi 981-1293, Japan. Electronic address: jyasuda@megabank.tohoku.ac.jp.
³ Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan.
⁴ Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan; Tohoku University Graduate School of Information Science, 6-3-09 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan.
⁵ Tohoku University Graduate School of Information Science, 6-3-09 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan.
⁶ Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan; Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
⁷ Department of Dermatology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621 Japan. Electronic address: rokuyama@shinshu-u.ac.jp.

PMID: 31023612
DOI: 10.1016/j.jdermsci.2019.03.006

Abstract

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.

Keywords: Chromosomal copy number alteration; ERBB2; Exome; Extramammary Paget disease; PIK3CA; TP53.

Publication types

Case Reports

MeSH terms

Aged
Biomarkers, Tumor / genetics*
Chromosome Aberrations*
Class I Phosphatidylinositol 3-Kinases / genetics
DNA Mutational Analysis
Exome / genetics
Exome Sequencing
Female
Humans
Male
Middle Aged
Mutation
Paget Disease, Extramammary / genetics*
Paget Disease, Extramammary / pathology
Polymorphism, Single Nucleotide
Rare Diseases / genetics*
Rare Diseases / pathology
Receptor, ErbB-2 / genetics
Skin Neoplasms / genetics*
Skin Neoplasms / pathology
Tumor Suppressor Protein p53 / genetics

Substances

Biomarkers, Tumor
TP53 protein, human
Tumor Suppressor Protein p53
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
ERBB2 protein, human
Receptor, ErbB-2