Massively parallel sequencing analysis of mucinous ovarian carcinomas: genomic profiling and differential diagnoses

Mueller, Jennifer J.; Schlappe, Brooke A.; Kumar, Rahul; Olvera, Narciso; Abu‐Rustum, Nadeem R.; Aghajanian, Carol; DeLair, Deborah F.; Hussein, Youssef; Soslow, Robert A.; Levine, Douglas A.; Weigelt, Britta

doi:10.1016/j.ygyno.2018.05.008

Cited by 43 publications

(29 citation statements)

References 40 publications

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“…It was reported that 79.0% of MC and 0.6% of HGSC have KRAS mutation. 25 Recently, KRAS mutation was found in 42% of EC. 24 Although KRAS is the most frequently mutated oncogene in human cancers, no therapeutic agent directly targeting RAS has yet been approved.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

et al. 2020

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“…Comparison of our primary mucinous ovarian cancer cohort with other mucin-producing malignancies identified significant differences in the mutational profiles of all histologies except that of mucinous pancreatic carcinoma. Our previous study also highlighted the clinical value of using molecular profiling to diagnose primary mucinous ovarian cancer and identify potentially targetable mutations and copy number alterations 17. A recently published paper by Meagher et al advocates for molecular profiling of mucinous ovarian cancer of uncertain primary origin.…”

Section: Discussionmentioning

confidence: 82%

A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen

Schlappe

Zhou

O’Cearbhaill

et al. 2019

Int J Gynecol Cancer

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ObjectiveWe described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens.MethodsWe identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher’s exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis.ResultsOf 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25–68) gynecologic cohort, 38 (range 32–68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2 (range 18–31) gynecologic cohort, 23 kg/m2 (range 18–31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal.ConclusionOngoing international collaborative research may further define associations between chemotherapy regimens and survival.

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“…Recently, it has been reported that lack of Cdkn2a in V600E BRAF mutated melanocytes in rodents is associated with rare progression to melanoma [40]. In MOC, Cdkn2a/b homozygous deletions/mutations were detected at high frequencies [41]. From these reports, it appears that loss of Cdkn2a in mucinous ovarian tumors with V600E BRAF mutation impairs progression to carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Mucinous borderline ovarian tumors with BRAFV600E mutation may have low risk for progression to invasive carcinomas

Ohnishi

Nakayama

Ishikawa

et al. 2020

Arch Gynecol Obstet

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Purpose Mucinous ovarian carcinomas (MOCs) are relatively rare. It has been proposed that a subset of mucinous cystadenomas (MCAs) may progress to mucinous borderline tumors (MBTs), and then to MOCs. KRAS is the predominantly mutated gene in MOC; however, other associated mutations and the mechanism underlying carcinogenesis in MOC remain unclear. Here, we assessed molecular genetic alterations in mucinous ovarian tumors and constructed mutation profiles. Methods Using the Sanger sequencing method, we assessed genetic mutations (KRAS, BRAF, TP53, and PIK3CA) in 16 cases of MOC, 10 cases of MBT, and 12 cases of MCA. Results Among MOC cases, the prevalence of G12D and G13D KRAS mutations was 43.8% (7/16). No MOC cases showed V600E BRAF and TP53 mutations. Among MBT cases, the prevalence of G12D KRAS mutation was 20.0% (2/10), those of TP53 and PIK3CA mutations were nil, and that of V600E BRAF mutation was 40% (4/10). None of the genetic mutations assessed were detected among MCA cases. Conclusion These results suggest that MBT with V600E BRAF mutation may rarely progress to MOC, while MBT with G12D or G13D KRAS mutation may more commonly progress to MOC.

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Massively parallel sequencing analysis of mucinous ovarian carcinomas: genomic profiling and differential diagnoses

Abstract: Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC.

Cited by 43 publications

References 40 publications

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors

A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen

Mucinous borderline ovarian tumors with BRAFV600E mutation may have low risk for progression to invasive carcinomas

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