Massively parallel sequencing analysis of mucinous ovarian carcinomas: Genomic profiling and differential diagnoses Journal Article


Authors: Mueller, J. J.; Schlappe, B. A.; Kumar, R.; Olvera, N.; Dao, F.; Abu-Rustum, N.; Aghajanian, C.; DeLair, D.; Hussein, Y. R.; Soslow, R. A.; Levine, D. A.; Weigelt, B.
Article Title: Massively parallel sequencing analysis of mucinous ovarian carcinomas: Genomic profiling and differential diagnoses
Abstract: Objective: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer resistant to standard chemotherapy regimens. We sought to characterize the repertoire of somatic mutations in MOCs and to define the contribution of massively parallel sequencing to the classification of tumors diagnosed as primary MOCs. Methods: Following gynecologic pathology and chart review, DNA samples obtained from primary MOCs and matched normal tissues/blood were subjected to whole-exome (n = 9) or massively parallel sequencing targeting 341 cancer genes (n = 15). Immunohistochemical analysis of estrogen receptor, progesterone receptor, PTEN, ARID1A/BAF250a, and the DNA mismatch (MMR) proteins MSH6 and PMS2 was performed for all cases. Mutational frequencies of MOCs were compared to those of high-grade serous ovarian cancers (HGSOCs) and mucinous tumors from other sites. Results: MOCs were heterogeneous at the genetic level, frequently harboring TP53 (75%) mutations, KRAS (71%) mutations and/or CDKN2A/B homozygous deletions/mutations (33%). Although established criteria for diagnosis were employed, four cases harbored mutational and immunohistochemical profiles similar to those of endometrioid carcinomas, and one case for colorectal or endometrioid carcinoma. Significant differences in the frequencies of KRAS, TP53, CDKN2A, FBXW7, PIK3CA and/or APC mutations between the confirmed primary MOCs (n = 19) and HGSOCs, mucinous gastric and/or mucinous colorectal carcinomas were found, whereas no differences in the 341 genes studied between MOCs and mucinous pancreatic carcinomas were identified. Conclusions: 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. © 2018 Elsevier Inc.
Keywords: immunohistochemistry; classification; diagnosis; massively parallel sequencing; mucinous ovarian cancer
Journal Title: Gynecologic Oncology
Volume: 150
Issue: 1
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2018-07-01
Start Page: 127
End Page: 135
Language: English
DOI: 10.1016/j.ygyno.2018.05.008
PROVIDER: scopus
PUBMED: 29793804
DOI/URL:
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Douglas A Levine
    357 Levine
  2. Robert Soslow
    655 Soslow
  3. Narciso Olvera
    71 Olvera
  4. Deborah F DeLair
    91 DeLair
  5. Fanny Dao
    56 Dao
  6. Yaser Raji Hussein
    45 Hussein
  7. Britta Weigelt
    264 Weigelt
  8. Jennifer Jean Mueller
    28 Mueller
  9. Rahul Kumar
    13 Kumar