Spectrum of SMARCB1/INI1 Mutations in Familial and Sporadic Rhabdoid Tumors

被引:259
作者
Eaton, Katherine W. [1 ]
Tooke, Laura S. [2 ]
Wainwright, Luanne M. [2 ]
Judkins, Alexander R. [2 ,3 ]
Biegel, Jaclyn A. [1 ,2 ,4 ]
机构
[1] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
关键词
INI1; rhabdoid; schwannomatosis SMARCB1; GERM-LINE MOSAICISM; INI1; EXPRESSION; RETINOBLASTOMA GENE; SUPPRESSOR GENE; HSNF5/INI1; SCHWANNOMATOSIS; CANCER; INI1/SMARCB1; FEATURES; SARCOMAS;
D O I
10.1002/pbc.22831
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Germline mutations and deletions of SMARCB1/INI1 in chromosome band 22q11 2 predispose patients to rhabdoid tumor and schwannomatosis Previous estimates suggested that 15-20% of rhabdoid tumors were caused by an underlying germline abnormality of SMARCB1 However, these studies were limited by case selection and an inability to detect intragenic deletions and duplications Procedure One hundred matched tumor and blood samples from patients with rhabdoid tumors of the brain kidney or soft tissues were analyzed for mutations and deletions of SMARCB1 by FISH multiplex ligation dependent probe amplification (MLPA), sequence analysis and high resolution Illumina 610K SNP based oligonucleotide array studies Results Thirty five of 100 patients were found to have a germline SMARCB1 abnormality These abnormalities included point and frameshift mutations intragenic deletions and duplications and larger deletions including regions both proximal and distal to SMARCB1 There were nine cases that demonstrated parent to child transmission of a mutated copy of SMARCB1 In eight of the nine cases one or more family members were also diagnosed with rhabdoid tumor or schwannoma, and two of the eight families presented with multiple affected children in a manner consistent with gonadal mosaicism Conclusions Approximately one third of newly diagnosed patients with rhabdoid tumor have an underlying genetic predisposition to tumors due to a germline SMARCB1 alteration Families may demonstrate incomplete penetrance and gonadal mosaicism which must be considered when counseling families of patients with rhabdoid tumor Pediatr Blood Cancer 2011,56 7-15 (C) 2010 Wiley Liss Inc
引用
收藏
页码:7 / 15
页数:9
相关论文
共 30 条
[1]  
Biegel JA, 1999, CANCER RES, V59, P74
[2]   hSNFS/INII-deficient tumours and rhabdoid tumours are convergent but not fully overlapping entities [J].
Bourdeaut, F. ;
Freneaux, P. ;
Thuille, B. ;
Lellouch-Tubiana, A. ;
Nicolas, A. ;
Couturier, J. ;
Pierron, G. ;
Sainte-Rose, C. ;
Bergeron, C. ;
Bouvier, R. ;
Rialland, X. ;
Laurence, V. ;
Michon, J. ;
Sastre-Garau, X. ;
Delattre, O. .
JOURNAL OF PATHOLOGY, 2007, 211 (03) :323-330
[3]   Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis [J].
Boyd, C. ;
Smith, M. J. ;
Kluwe, L. ;
Balogh, A. ;
MacCollin, M. ;
Plotkin, S. R. .
CLINICAL GENETICS, 2008, 74 (04) :358-366
[4]   Clinicopathologic Comparison of Familial Versus Sporadic Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System [J].
Bruggers, Carol S. ;
Bleyl, Steven B. ;
Pysher, Theodore ;
Barnette, Philip ;
Afify, Zeinab ;
Walker, Marion ;
Biegel, Jaclyn A. .
PEDIATRIC BLOOD & CANCER, 2011, 56 (07) :1026-1031
[5]   Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior [J].
Cheng, Jason X. ;
Tretiakova, Maria ;
Gong, Can ;
Mandal, Saptarshi ;
Krausz, Thomas ;
Taxy, Jerome B. .
MODERN PATHOLOGY, 2008, 21 (06) :647-652
[6]   One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma [J].
Corson, Timothy W. ;
Gallie, Brenda L. .
GENES CHROMOSOMES & CANCER, 2007, 46 (07) :617-634
[7]   Loss of INI1 Expression is Characteristic of Both Conventional and Proximal-type Epithelioid Sarcoma [J].
Hornick, Jason L. ;
Dal Cin, Paola ;
Fletcher, Christopher D. M. .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2009, 33 (04) :542-550
[8]   SMARCB1/INI1 maternal germ line mosaicism in schwannomatosis [J].
Hulsebos, T. J. M. ;
Kenter, S. B. ;
Jakobs, M. E. ;
Baas, F. ;
Chong, B. ;
Delatycki, M. B. .
CLINICAL GENETICS, 2010, 77 (01) :86-91
[9]   Germline mutation of INI1/SMARCB1 in familial schwannomatosis [J].
Hulsebos, Theo J. M. ;
Plomp, Astrid S. ;
Wolterman, Ruud A. ;
Robanus-Maandag, Els C. ;
Baas, Frank ;
Wesseling, Pieter .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (04) :805-810
[10]   High-density single nucleotide polymorphism array analysis in patients with germline deletions of 22q11.2 and malignant rhabdoid tumor [J].
Jackson, Eric M. ;
Shaikh, Tamim H. ;
Gururangan, Sridharan ;
Jones, Marilyn C. ;
Malkin, David ;
Nikkel, Sarah M. ;
Zuppan, Craig W. ;
Wainwright, Luanne M. ;
Zhang, Fan ;
Biegel, Jaclyn A. .
HUMAN GENETICS, 2007, 122 (02) :117-127