Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?

被引：45
作者：
Cervigne, Nilva K. [1 ,5 ]
Machado, Jerry [6 ,10 ]
Goswami, Rashmi S. [6 ,11 ]
Sadikovic, Bekim [12 ]
Bradley, Grace [1 ,7 ]
Perez-Ordonez, Bayardo [2 ]
Naranjo Galloni, Natalie [13 ]
Gilbert, Ralph [14 ,15 ]
Gullane, Patrick [14 ,15 ]
Irish, Jonathan C. [14 ,15 ]
Jurisica, Igor [3 ,4 ,8 ,9 ]
Reis, Patricia P. [1 ,16 ]
Kamel-Reid, Suzanne [1 ,2 ,6 ]
机构：
[1] Ontario Canc Inst, Div Appl Mol Oncol, Toronto, ON M4X 1K9, Canada
[2] Toronto Gen Hosp, Ontario Canc Inst, Dept Pathol, Toronto, ON, Canada
[3] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada
[4] Univ Hlth Network, Techna Inst, Toronto, ON M5G 2M9, Canada
[5] Univ Estadual Campinas, Fac Dent FOP, Dept Oral Diagnost, Piracicaba, SP, Brazil
[6] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[7] Univ Toronto, Fac Dent, Toronto, ON, Canada
[8] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
[9] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada
[10] Prevent Genet, Marshfield, WI USA
[11] Vancouver Gen Hosp, Dept Hematopathol, Vancouver, BC, Canada
[12] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada
[13] Hosp Calderon Guardia, Dept Otolaryngol, San Jose, Costa Rica
[14] Univ Toronto, Princess Margaret Hosp, Dept Otolaryngol Surg Oncol, Toronto, ON, Canada
[15] Univ Hlth Network, Toronto, ON M5G 2M9, Canada
[16] Sao Paulo State Univ UNESP, Fac Med, Dept Surg & Orthoped, Botucatu, SP, Brazil
来源：
HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 10期
基金：
加拿大创新基金会;
关键词：
SQUAMOUS-CELL CARCINOMAS; COPY NUMBER; ABERRANT EXPRESSION; NECK-CANCER; ARRAY-CGH; KAPPA-B; GENE; HEAD; HYBRIDIZATION; AMPLIFICATION;
D O I：
10.1093/hmg/ddt657
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A significant proportion (up to 62) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68), 9q34.13 (64), 21q22.3 (60), 6p21 and 6q25 (56) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48). DNA losses were observed in 20 of samples and mainly detected on 5q31.2 (35), 16p13.2 (30), 9q33.1 and 9q33.29 (25) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70 of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Proteinprotein interaction networks were created to identify possible pathways associated with OSCC progression.
引用
收藏
页码：2618 / 2628
页数：11
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