Whole exome sequencing of adenoid cystic carcinoma

P.J. Stephens; H.R. Davies; Y. Mitani; P. Van Loo; A. Shlien; P.S. Tarpey; E. Papaemmanuil; A. Cheverton; G.R. Bignell; A.P. Butler; J. Gamble; S. Gamble; C. Hardy; J. Hinton; M. Jia; A. Jayakumar; D. Jones; C. Latimer; S. McLaren; D.J. McBride; A. Menzies; L. Mudie; M. Maddison; K. Raine; S. Nik-Zainal; S. O'Meara; J.W. Teague; I. Varela; D.C. Wedge; I. Whitmore; S.M. Lippman; U. McDermott; M.R. Stratton; P.J. Campbell; A.K. El-Naggar; P.A. Futreal

doi:10.1172/JCI67201

Whole exome sequencing of adenoid cystic carcinoma

P.J. Stephens, H.R. Davies, Y. Mitani, P. Van Loo, A. Shlien, P.S. Tarpey, E. Papaemmanuil, A. Cheverton, G.R. Bignell, A.P. Butler, J. Gamble, S. Gamble, C. Hardy, J. Hinton, M. Jia, A. Jayakumar, D. Jones, C. Latimer, S. McLaren, D.J. McBrideA. Menzies, L. Mudie, M. Maddison, K. Raine, S. Nik-Zainal, S. O'Meara, J.W. Teague, I. Varela, D.C. Wedge, I. Whitmore, S.M. Lippman, U. McDermott, M.R. Stratton, P.J. Campbell, A.K. El-Naggar, P.A. Futreal

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.

Original language	English
Pages (from-to)	2965-2968
Number of pages	4
Journal	Journal of Clinical Investigation
Volume	123
Issue number	7
DOIs	https://doi.org/10.1172/JCI67201
Publication status	Published - Jul 2013

Keywords

Carcinoma
Adenoid cystic carcinoma
DNA Mutational Analysis
Exome
Genes

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1172/JCI67201

Cite this

Stephens, P. J., Davies, H. R., Mitani, Y., Van Loo, P., Shlien, A., Tarpey, P. S., Papaemmanuil, E., Cheverton, A., Bignell, G. R., Butler, A. P., Gamble, J., Gamble, S., Hardy, C., Hinton, J., Jia, M., Jayakumar, A., Jones, D., Latimer, C., McLaren, S., ... Futreal, P. A. (2013). Whole exome sequencing of adenoid cystic carcinoma. Journal of Clinical Investigation, 123(7), 2965-2968. https://doi.org/10.1172/JCI67201

@article{3dac33b62efa4f93b1ea0b95318dd1c8,

title = "Whole exome sequencing of adenoid cystic carcinoma",

abstract = "Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.",

keywords = "Carcinoma, Adenoid cystic carcinoma, DNA Mutational Analysis, Exome, Genes",

author = "P.J. Stephens and H.R. Davies and Y. Mitani and {Van Loo}, P. and A. Shlien and P.S. Tarpey and E. Papaemmanuil and A. Cheverton and G.R. Bignell and A.P. Butler and J. Gamble and S. Gamble and C. Hardy and J. Hinton and M. Jia and A. Jayakumar and D. Jones and C. Latimer and S. McLaren and D.J. McBride and A. Menzies and L. Mudie and M. Maddison and K. Raine and S. Nik-Zainal and S. O'Meara and J.W. Teague and I. Varela and D.C. Wedge and I. Whitmore and S.M. Lippman and U. McDermott and M.R. Stratton and P.J. Campbell and A.K. El-Naggar and P.A. Futreal",

year = "2013",

month = jul,

doi = "10.1172/JCI67201",

language = "English",

volume = "123",

pages = "2965--2968",

journal = "Journal of Clinical Investigation",

issn = "1558-8238",

publisher = "American Society for Clinical Investigation",

number = "7",

}

Stephens, PJ, Davies, HR, Mitani, Y, Van Loo, P, Shlien, A, Tarpey, PS, Papaemmanuil, E, Cheverton, A, Bignell, GR, Butler, AP, Gamble, J, Gamble, S, Hardy, C, Hinton, J, Jia, M, Jayakumar, A, Jones, D, Latimer, C, McLaren, S, McBride, DJ, Menzies, A, Mudie, L, Maddison, M, Raine, K, Nik-Zainal, S, O'Meara, S, Teague, JW, Varela, I, Wedge, DC, Whitmore, I, Lippman, SM, McDermott, U, Stratton, MR, Campbell, PJ, El-Naggar, AK & Futreal, PA 2013, 'Whole exome sequencing of adenoid cystic carcinoma', Journal of Clinical Investigation, vol. 123, no. 7, pp. 2965-2968. https://doi.org/10.1172/JCI67201

TY - JOUR

T1 - Whole exome sequencing of adenoid cystic carcinoma

AU - Stephens, P.J.

AU - Davies, H.R.

AU - Mitani, Y.

AU - Van Loo, P.

AU - Shlien, A.

AU - Tarpey, P.S.

AU - Papaemmanuil, E.

AU - Cheverton, A.

AU - Bignell, G.R.

AU - Butler, A.P.

AU - Gamble, J.

AU - Gamble, S.

AU - Hardy, C.

AU - Hinton, J.

AU - Jia, M.

AU - Jayakumar, A.

AU - Jones, D.

AU - Latimer, C.

AU - McLaren, S.

AU - McBride, D.J.

AU - Menzies, A.

AU - Mudie, L.

AU - Maddison, M.

AU - Raine, K.

AU - Nik-Zainal, S.

AU - O'Meara, S.

AU - Teague, J.W.

AU - Varela, I.

AU - Wedge, D.C.

AU - Whitmore, I.

AU - Lippman, S.M.

AU - McDermott, U.

AU - Stratton, M.R.

AU - Campbell, P.J.

AU - El-Naggar, A.K.

AU - Futreal, P.A.

PY - 2013/7

Y1 - 2013/7

N2 - Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.

AB - Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.

KW - Carcinoma

KW - Adenoid cystic carcinoma

KW - DNA Mutational Analysis

KW - Exome

KW - Genes

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84879627051&partnerID=MN8TOARS

U2 - 10.1172/JCI67201

DO - 10.1172/JCI67201

M3 - Article

SN - 1558-8238

VL - 123

SP - 2965

EP - 2968

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 7

ER -

Whole exome sequencing of adenoid cystic carcinoma

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this