Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors

Georgina L Ryland, Sally M Hunter, Maria A Doyle, Franco Caramia, Jason Li, Simone M Rowley, Michael Christie, Prue E Allan, Andrew Stephens, David D L Bowtell, Ian G Campbell, Kylie Louise Gorringe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date. METHODS: To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53. RESULTS: The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 ), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5. CONCLUSIONS: The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.
Original languageEnglish
Article number87
Number of pages12
JournalGenome Medicine: medicine in the post-genomic era
Volume7
Issue number1
DOIs
Publication statusPublished - 2015

Cite this

Ryland, G. L., Hunter, S. M., Doyle, M. A., Caramia, F., Li, J., Rowley, S. M., ... Gorringe, K. L. (2015). Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. Genome Medicine: medicine in the post-genomic era, 7(1), [87]. https://doi.org/10.1186/s13073-015-0210-y
Ryland, Georgina L ; Hunter, Sally M ; Doyle, Maria A ; Caramia, Franco ; Li, Jason ; Rowley, Simone M ; Christie, Michael ; Allan, Prue E ; Stephens, Andrew ; Bowtell, David D L ; Campbell, Ian G ; Gorringe, Kylie Louise. / Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. In: Genome Medicine: medicine in the post-genomic era. 2015 ; Vol. 7, No. 1.
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abstract = "Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date. METHODS: To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53. RESULTS: The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 ), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5. CONCLUSIONS: The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.",
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Ryland, GL, Hunter, SM, Doyle, MA, Caramia, F, Li, J, Rowley, SM, Christie, M, Allan, PE, Stephens, A, Bowtell, DDL, Campbell, IG & Gorringe, KL 2015, 'Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors' Genome Medicine: medicine in the post-genomic era, vol. 7, no. 1, 87. https://doi.org/10.1186/s13073-015-0210-y

Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. / Ryland, Georgina L; Hunter, Sally M; Doyle, Maria A; Caramia, Franco; Li, Jason; Rowley, Simone M; Christie, Michael; Allan, Prue E; Stephens, Andrew; Bowtell, David D L; Campbell, Ian G; Gorringe, Kylie Louise.

In: Genome Medicine: medicine in the post-genomic era, Vol. 7, No. 1, 87, 2015.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors

AU - Ryland, Georgina L

AU - Hunter, Sally M

AU - Doyle, Maria A

AU - Caramia, Franco

AU - Li, Jason

AU - Rowley, Simone M

AU - Christie, Michael

AU - Allan, Prue E

AU - Stephens, Andrew

AU - Bowtell, David D L

AU - Campbell, Ian G

AU - Gorringe, Kylie Louise

PY - 2015

Y1 - 2015

N2 - Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date. METHODS: To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53. RESULTS: The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 ), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5. CONCLUSIONS: The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.

AB - Mucinous ovarian tumors are an unusual group of rare neoplasms with an apparently clear progression from benign to borderline to carcinoma, yet with a controversial cell of origin in the ovarian surface epithelium. They are thought to be molecularly distinct from other ovarian tumors but there have been no exome-level sequencing studies performed to date. METHODS: To understand the genetic etiology of mucinous ovarian tumors and assess the presence of novel therapeutic targets or pathways, we undertook exome sequencing of 24 tumors encompassing benign (5), borderline (8) and carcinoma (11) histologies and also assessed a validation cohort of 58 tumors for specific gene regions including exons 4-9 of TP53. RESULTS: The predominant mutational signature was of C>T transitions in a NpCpG context, indicative of deamination of methyl-cytosines. As well as mutations in known drivers (KRAS, BRAF and CDKN2A), we identified a high percentage of carcinomas with TP53 mutations (52 ), and recurrent mutations in RNF43, ELF3, GNAS, ERBB3 and KLF5. CONCLUSIONS: The diversity of mutational targets suggests multiple routes to tumorigenesis in this heterogeneous group of tumors that is generally distinct from other ovarian subtypes.

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JO - Genome Medicine: medicine in the post-genomic era

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SN - 1756-994X

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