Yukiko Kiniwa1, Jun Yasuda2, Sakae Saito3, Rumiko Saito3, Ikuko N Motoike4, Inaho Danjoh3, Kengo Kinoshita5, Nobuo Fuse3, Masayuki Yamamoto6, Ryuhei Okuyama7. 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.
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.
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.
Authors: Marina Stasenko; Gowtham Jayakumaran; Renee Cowan; Vance Broach; Dennis S Chi; Anthony Rossi; Travis J Hollman; Ahmet Zehir; Nadeem R Abu-Rustum; Mario M Leitao Journal: JCO Precis Oncol Date: 2020-09-15
Authors: Zoran Gatalica; Semir Vranic; Božo Krušlin; Kelsey Poorman; Phillip Stafford; Denisa Kacerovska; Wijendra Senarathne; Elena Florento; Elma Contreras; Alexandra Leary; April Choi; Gino K In Journal: Cancer Med Date: 2020-01-03 Impact factor: 4.452