ALK germline mutations in patients with neuroblastorna: a rare and weakly penetrant syndrome

被引：33

作者：

Bourdeaut, Franck ^{[1
,2
,3
]}

Ferrand, Sandrine ^{[4
]}

Brugieres, Laurence ^{[5
]}

Hilbert, Marjorie ^{[6
,7
]}

Ribeiro, Agnes ^{[4
]}

Lacroix, Ludovic ^{[8
]}

Benard, Jean ^{[8
]}

Combaret, Valerie ^{[9
]}

Michon, Jean ^{[2
]}

Valteau-Couanet, Dominique ^{[5
]}

Isidor, Bertrand ^{[10
]}

Rialland, Xavier ^{[11
]}

Poiree, Maryline ^{[12
]}

Defachelles, Anne-Sophie ^{[13
]}

Peuchmaur, Michel ^{[14
]}

Schleiermacher, Gudrun ^{[1
,2
]}

Pierron, Gaelle ^{[4
]}

Gauthier-Villars, Marion ^{[15
]}

Janoueix-Lerosey, Isabelle ^{[1
]}

Delattre, Olivier ^{[1
,4
]}

机构：

[1] Inst Curie, Lab Genet & Biol Canc, INSERMU830, F-75348 Paris 05, France

[2] Inst Curie, Dept Pediat, F-75348 Paris 05, France

[3] CHU Nantes, Serv Hematooncol Pediat, F-44035 Nantes 01, France

[4] Inst Curie, Unite Genet Somat, F-75348 Paris 05, France

[5] Inst Gustave Roussy, Dept Pediat, Villejuif, France

[6] Univ Bordeaux, Serv Hematooncol Pediat, Bordeaux, France

[7] CHU Bordeaux, Bordeaux, France

[8] Inst Gustave Roussy, Dept Biol & Pathol Med, Villejuif, France

[9] Ctr Leon Berard, Lab Rech Translat, F-69373 Lyon, France

[10] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France

[11] CHU Angers, Serv Hematooncol Pediat, Angers, France

[12] CHU Nice, Serv Hematooncol Pediat, Nice, France

[13] Ctr Oscar Lambret, Dept Pediat, F-59020 Lille, France

[14] Univ Paris 06, Hop Robert Debre, Serv Anat Pathol, Paris, France

[15] Inst Curie, Dept Oncogenet, F-75348 Paris 05, France

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2012年 / 20卷 / 03期

关键词：

ALK; neuroblastoma; predisposition; CENTRAL-HYPOVENTILATION-SYNDROME; FAMILIAL NEUROBLASTOMA; PHOX2B MUTATIONS; ACTIVATING MUTATIONS; ONCOGENIC MUTATIONS; HOMEOBOX GENE; CANCER; PHENOTYPE; PREDISPOSITION; RETINOBLASTOMA;

D O I：

10.1038/ejhg.2011.195

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：

Neuroblastic tumours may occur in a predisposition context. Two main genes are involved: PHOX2B, observed in familial cases and frequently associated with other neurocristopathies (Ondine's and Hirschsprung's disease); and ALK, mostly in familial tumours. We have assessed the frequency of mutations of these two genes in patients with a presumable higher risk of predisposition. We sequenced both genes in 26 perinatal cases (prebirth and <1 month of age, among which 10 were multifocal), 16 multifocal postnatal (>1 month) cases, 3 pairs of affected relatives and 8 patients with multiple malignancies. The whole coding sequences of the two genes were analysed in tumour and/or constitutional DNAs. We found three ALK germline mutations, all in a context of multifocal tumours. Two mutations (T1151R and R1192P) were inherited and shared by several unaffected patients, thus illustrating an incomplete penetrance. Younger age at tumour onset did not seem to offer a relevant selection criterion for ALK analyses. Conversely, multifocal tumours might be the most to benefit from the genetic screening. Finally, no PHOX2B germline mutation was found in this series. In conclusion, ALK deleterious mutations are rare events in patients with a high probability of predisposition. Other predisposing genes remain to be discovered. European Journal of Human Genetics (2012) 20, 291-297; doi:10.1038/ejhg.2011.195; published online 9 November 2011

引用

页码：291 / 297

页数：7

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