Massively parallel sequencing analysis of mucinous ovarian carcinomas: genomic profiling and differential diagnoses
| Autor: | Deborah DeLair, Rajesh Kumar, Nadeem R. Abu-Rustum, Narciso Olvera, Brooke A. Schlappe, Douglas A. Levine, Yaser R. Hussein, Britta Weigelt, Fanny Dao, Jennifer J. Mueller, Carol Aghajanian, Robert A. Soslow |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system diseases medicine.disease_cause Article Diagnosis Differential 03 medical and health sciences 0302 clinical medicine CDKN2A PMS2 Carcinoma Humans Medicine neoplasms Ovarian Neoplasms Massive parallel sequencing business.industry Obstetrics and Gynecology Genomics medicine.disease Immunohistochemistry MSH6 Serous fluid 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female KRAS business Ovarian cancer |
| Zdroj: | Gynecologic Oncology. 150:127-135 |
| ISSN: | 0090-8258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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