Germline SDHA mutations in children and adults with cancer

Marianne Dubard Gault; Diana Mandelker; Deborah Delair; Carolyn R. Stewart; Yelena Kemel; Margaret R. Sheehan; Beth Siegel; Jennifer Kennedy; Vanessa Marcell; Angela Arnold; Hikmat Al-Ahmadie; Shakeel Modak; Mark Robson; Neerav Shukla; Stephen Roberts; Joseph Vijai; Sabine Topka; Alex Kentsis; Karen Cadoo; Maria Carlo; Alicia Latham Schwark; Ed Reznik; Renzo Dinatale; Jaclyn Hechtman; Ester Borras Flores; Sowmaya Jairam; Ciyu Yang; Yirong Li; Erol Can Bayraktar; Ozge Ceyhan-Birsoy; Liying Zhang; Wendy Kohlman; Joshua Schiffman; Zsofia Stadler; Kivanc Birsoy; Andrew Kung; Kenneth Offit; Michael F. Walsh

doi:10.1101/mcs.a002584

Germline SDHA mutations in children and adults with cancer

Marianne Dubard Gault, Diana Mandelker, Deborah Delair, Carolyn R. Stewart, Yelena Kemel, Margaret R. Sheehan, Beth Siegel, Jennifer Kennedy, Vanessa Marcell, Angela Arnold, Hikmat Al-Ahmadie, Shakeel Modak, Mark Robson, Neerav Shukla, Stephen Roberts, Joseph Vijai, Sabine Topka, Alex Kentsis, Karen Cadoo, Maria CarloAlicia Latham Schwark, Ed Reznik, Renzo Dinatale, Jaclyn Hechtman, Ester Borras Flores, Sowmaya Jairam, Ciyu Yang, Yirong Li, Erol Can Bayraktar, Ozge Ceyhan-Birsoy, Liying Zhang, Wendy Kohlman, Joshua Schiffman, Zsofia Stadler, Kivanc Birsoy, Andrew Kung, Kenneth Offit, Michael F. Walsh

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Abstract

Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.

Original language	English (US)
Article number	a002584
Journal	Cold Spring Harbor Molecular Case Studies
Volume	4
Issue number	4
DOIs	https://doi.org/10.1101/mcs.a002584
State	Published - Aug 2018
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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Gault, M. D., Mandelker, D., Delair, D., Stewart, C. R., Kemel, Y., Sheehan, M. R., Siegel, B., Kennedy, J., Marcell, V., Arnold, A., Al-Ahmadie, H., Modak, S., Robson, M., Shukla, N., Roberts, S., Vijai, J., Topka, S., Kentsis, A., Cadoo, K., ... Walsh, M. F. (2018). Germline SDHA mutations in children and adults with cancer. Cold Spring Harbor Molecular Case Studies, 4(4), Article a002584. https://doi.org/10.1101/mcs.a002584

Gault, MD, Mandelker, D, Delair, D, Stewart, CR, Kemel, Y, Sheehan, MR, Siegel, B, Kennedy, J, Marcell, V, Arnold, A, Al-Ahmadie, H, Modak, S, Robson, M, Shukla, N, Roberts, S, Vijai, J, Topka, S, Kentsis, A, Cadoo, K, Carlo, M, Schwark, AL, Reznik, E, Dinatale, R, Hechtman, J, Flores, EB, Jairam, S, Yang, C, Li, Y, Bayraktar, EC, Ceyhan-Birsoy, O, Zhang, L, Kohlman, W, Schiffman, J, Stadler, Z, Birsoy, K, Kung, A, Offit, K & Walsh, MF 2018, 'Germline SDHA mutations in children and adults with cancer', Cold Spring Harbor Molecular Case Studies, vol. 4, no. 4, a002584. https://doi.org/10.1101/mcs.a002584

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title = "Germline SDHA mutations in children and adults with cancer",

abstract = "Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.",

author = "Gault, {Marianne Dubard} and Diana Mandelker and Deborah Delair and Stewart, {Carolyn R.} and Yelena Kemel and Sheehan, {Margaret R.} and Beth Siegel and Jennifer Kennedy and Vanessa Marcell and Angela Arnold and Hikmat Al-Ahmadie and Shakeel Modak and Mark Robson and Neerav Shukla and Stephen Roberts and Joseph Vijai and Sabine Topka and Alex Kentsis and Karen Cadoo and Maria Carlo and Schwark, {Alicia Latham} and Ed Reznik and Renzo Dinatale and Jaclyn Hechtman and Flores, {Ester Borras} and Sowmaya Jairam and Ciyu Yang and Yirong Li and Bayraktar, {Erol Can} and Ozge Ceyhan-Birsoy and Liying Zhang and Wendy Kohlman and Joshua Schiffman and Zsofia Stadler and Kivanc Birsoy and Andrew Kung and Kenneth Offit and Walsh, {Michael F.}",

note = "Publisher Copyright: {\textcopyright} 2018 Dubard Gault et al.",

year = "2018",

month = aug,

doi = "10.1101/mcs.a002584",

language = "English (US)",

volume = "4",

journal = "Cold Spring Harbor Molecular Case Studies",

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AU - Gault, Marianne Dubard

AU - Mandelker, Diana

AU - Delair, Deborah

AU - Stewart, Carolyn R.

AU - Kemel, Yelena

AU - Sheehan, Margaret R.

AU - Siegel, Beth

AU - Kennedy, Jennifer

AU - Marcell, Vanessa

AU - Arnold, Angela

AU - Al-Ahmadie, Hikmat

AU - Modak, Shakeel

AU - Robson, Mark

AU - Shukla, Neerav

AU - Roberts, Stephen

AU - Vijai, Joseph

AU - Topka, Sabine

AU - Kentsis, Alex

AU - Cadoo, Karen

AU - Carlo, Maria

AU - Schwark, Alicia Latham

AU - Reznik, Ed

AU - Dinatale, Renzo

AU - Hechtman, Jaclyn

AU - Flores, Ester Borras

AU - Jairam, Sowmaya

AU - Yang, Ciyu

AU - Li, Yirong

AU - Bayraktar, Erol Can

AU - Ceyhan-Birsoy, Ozge

AU - Zhang, Liying

AU - Kohlman, Wendy

AU - Schiffman, Joshua

AU - Stadler, Zsofia

AU - Birsoy, Kivanc

AU - Kung, Andrew

AU - Offit, Kenneth

AU - Walsh, Michael F.

PY - 2018/8

Y1 - 2018/8

N2 - Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.

AB - Mutations in succinate dehydrogenase complex genes predispose to familial paraganglioma-pheochromocytoma syndrome (FPG) and gastrointestinal stromal tumors (GIST). Here we describe cancer patients undergoing agnostic germline testing at Memorial Sloan Kettering Cancer Center and found to harbor germline SDHA mutations. Using targeted sequencing covering the cancer census genes, we identified 10 patients with SDHA germline mutations. Cancer diagnoses for these patients carrying SDHA germline mutations included neuroblastoma (n = 1), breast (n = 1), colon (n = 1), renal (n = 1), melanoma and uterine (n = 1), prostate (n = 1), endometrial (n = 1), bladder (n = 1), and gastrointestinal stromal tumor (GIST) (n = 2). Immunohistochemical staining and assessment of patient tumors for second hits and loss of heterozygosity in SDHA confirmed GIST as an SDHA-associated tumor and suggests SDHA germline mutations may be a driver in neuroblastoma tumorigenesis.

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Germline SDHA mutations in children and adults with cancer

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