Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma

Deyin Xing, Yohan Suryo Rahmanto, Felix Zeppernick, Charlotte G. Hannibal, Susanne K. Kjaer, Russell S Vang, Ie Ming Shih, Tian-Li Wang

Research output: Contribution to journalArticle

Abstract

Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of SBT to invasive low-grade serous carcinoma (LGSC) remains largely unknown. Although mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor, noninvasive LGSC, or invasive LGSC. Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBTs (atypical proliferative serous tumors) or noninvasive LGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wild-type pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic events that drive LGSC progression are warranted.

Original languageEnglish (US)
Pages (from-to)87-91
Number of pages5
JournalHuman Pathology
Volume68
DOIs
StatePublished - Oct 1 2017

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Carcinoma
Mutation
Neoplasms
Oncogenes
Exons

Keywords

  • Low-grade serous carcinoma
  • NRAS mutation
  • Oncogenic driver
  • Ovarian cancer
  • RAS signaling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma. / Xing, Deyin; Suryo Rahmanto, Yohan; Zeppernick, Felix; Hannibal, Charlotte G.; Kjaer, Susanne K.; Vang, Russell S; Shih, Ie Ming; Wang, Tian-Li.

In: Human Pathology, Vol. 68, 01.10.2017, p. 87-91.

Research output: Contribution to journalArticle

Xing, Deyin ; Suryo Rahmanto, Yohan ; Zeppernick, Felix ; Hannibal, Charlotte G. ; Kjaer, Susanne K. ; Vang, Russell S ; Shih, Ie Ming ; Wang, Tian-Li. / Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma. In: Human Pathology. 2017 ; Vol. 68. pp. 87-91.
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abstract = "Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of SBT to invasive low-grade serous carcinoma (LGSC) remains largely unknown. Although mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor, noninvasive LGSC, or invasive LGSC. Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6{\%}) cases. The same mutation was not detected in any of the SBTs (atypical proliferative serous tumors) or noninvasive LGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wild-type pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic events that drive LGSC progression are warranted.",
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AU - Kjaer, Susanne K.

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