Genomic landscape of multiple Bowen's disease using whole-exome sequencing

被引:2
作者
Kim, Yoon-Seob [1 ,2 ,3 ]
Park, Gyeong Sin [4 ]
Bang, Chul Hwan [5 ]
Chung, Yeun-Jun [1 ,2 ,3 ]
机构
[1] Catholic Univ Korea, Coll Med, Precis Med Res Ctr, 222 Banpo Daero, Seoul 06591, South Korea
[2] Catholic Univ Korea, Coll Med, IRCGP, Seoul, South Korea
[3] Catholic Univ Korea, Coll Med, Dept Microbiol, Seoul, South Korea
[4] Catholic Univ Korea, Dept Hosp Pathol, Coll Med, Seoul St Marys Hosp, Seoul, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Dermatol, Seoul St Marys Hosp, 222 Banpo Daero, Seoul 06591, South Korea
基金
新加坡国家研究基金会;
关键词
Bowen disease; copy number alteration; mutation; next-generation sequencing; squamous cell carcinoma; BOWENS-DISEASE; MUTATIONS;
D O I
10.1111/1346-8138.16584
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The genomic landscape of Bowen's disease (BD), with multiple manifestations, has not yet been determined. This study aimed to investigate the genomic alterations in multiple BD. We performed whole-exome sequencing of BD lesions (n = 9) and matched germlines collected from three patients with multiple (>= 3) BD to detect somatic and germline mutations. We found a median of 64 somatic mutations in each sample (range 20-267). UV-signature mutations accounted for 64.9% (median, range 26.0%-82.1%) of point mutations. Putative driver mutations were found in five BDs (RB1 p.R445*, ARID2 p.R274*, TP53 p.Y163D/p.Y205D/p.R342*, KMT2C p.R4549C) but not in the other four lesions. Somatic mutations were not shared between multiple BD lesions collected from the same patient, indicating a different clonal origin. We also found no known pathogenic germline mutations in cancer-related genes. The mutational signature analysis revealed that UV signatures (SBS7a/7b) and age-related signatures (SBS1/5) were the main active signatures. Copy number alterations (CNAs) were found in two BDs: one with extensive CNA regions (21.7% of the genome), including driver genes (PIK3CA/SOX2/TP63 and MYC gain, and CDKN2A loss), and the other with 1q gain. Our study revealed that multiple BD lesions harbor distinct genomic landscapes, suggesting that they have different risks of malignant progression.
引用
收藏
页码:397 / 400
页数:4
相关论文
共 14 条
  • [1] UV Signature Mutations
    Brash, Douglas E.
    [J]. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2015, 91 (01) : 15 - 26
  • [2] The landscape of driver mutations in cutaneous squamous cell carcinoma
    Chang, Darwin
    Shain, A. Hunter
    [J]. NPJ GENOMIC MEDICINE, 2021, 6 (01)
  • [3] Squamous Cell Cancers: A Unified Perspective on Biology and Genetics
    Dotto, G. Paolo
    Rustgi, Anil K.
    [J]. CANCER CELL, 2016, 29 (05) : 622 - 637
  • [4] Germ line TP53 mutation in a patient with multiple Bowen's disease
    Hatta, Naohito
    Hatta, Yuri
    [J]. JOURNAL OF DERMATOLOGY, 2019, 46 (06) : E198 - E200
  • [5] Islam S.M.A., 2022, BIORXIV, DOI [10.1101/2020.12.13.422570v3, DOI 10.1101/2020.12.13.422570V3]
  • [6] Genomic Progression of Precancerous Actinic Keratosis to Squamous Cell Carcinoma
    Kim, Yoon-Seob
    Shin, Sun
    Jung, Seung-Hyun
    Park, Young Min
    Park, Gyeong Sin
    Lee, Sug Hyung
    Chung, Yeun-Jun
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2022, 142 (3 PT A) : 528 - +
  • [7] VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing
    Koboldt, Daniel C.
    Zhang, Qunyuan
    Larson, David E.
    Shen, Dong
    McLellan, Michael D.
    Lin, Ling
    Miller, Christopher A.
    Mardis, Elaine R.
    Ding, Li
    Wilson, Richard K.
    [J]. GENOME RESEARCH, 2012, 22 (03) : 568 - 576
  • [8] Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes
    Lazo de la Vega, Lorena
    Bick, Nolan
    Hu, Kevin
    Rahrig, Samantha E.
    Silva, Camilla Duarte
    Matayoshi, Suzana
    Picciarelli, Patricia
    Wang, Xiaoming
    Sugar, Alan
    Soong, Hunson Kaz
    Mian, Shahzad I.
    Robinson, Dan R.
    Chinnaiyan, Arul M.
    Demirci, Hakan
    Daniels, Anthony B.
    Worden, Francis
    Eberhart, Charles G.
    Tomlins, Scott A.
    Rao, Rajesh C.
    Harms, Paul W.
    [J]. MODERN PATHOLOGY, 2020, 33 (11) : 2280 - 2294
  • [9] p53 gene mutations in Bowen's disease in Koreans:: clustering in exon 5 and multiple mutations
    Lee, HJ
    Kim, JS
    Ha, SJ
    Roh, KY
    Seo, EJ
    Park, WS
    Lee, JY
    Park, KS
    Kim, JW
    [J]. CANCER LETTERS, 2000, 158 (01) : 27 - 33
  • [10] British Association of Dermatologists' guidelines for the management of squamous cell carcinoma in situ (Bowen's disease) 2014
    Morton, C. A.
    Birnie, A. J.
    Eedy, D. J.
    [J]. BRITISH JOURNAL OF DERMATOLOGY, 2014, 170 (02) : 245 - 260