Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation

A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 9357924, 2 pages https://doi.org/10.1155/2019/9357924 Case Report A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation 1 2 1 Adamantia Nikolaidi , Irene Konstantopoulou , Nikolaos Pistalmantzian, 2 2 1 Florentia Fostira , Drakoulis Yannoukakos, and Ilias Athanasiadis Oncology Department MITERA Hospital, Athens, Greece Molecular Diagnostics Lab, NCSR “Demokritos”, Athens, Greece Correspondence should be addressed to Adamantia Nikolaidi; mantonikolaidi@gmail.com Received 13 February 2019; Accepted 24 March 2019; Published 16 May 2019 Academic Editor: Jose I. Mayordomo Copyright © 2019 Adamantia Nikolaidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of a 58-year-old female with ovarian cancer. The patient presented with ascites, and the biopsies revealed a low-grade adenocarcinoma, either a serous papillary ovarian cancer with peritoneal implants or a primary peritoneal carcinoma. She received neoadjuvant chemotherapy and after 5 cycles achieved partial response, and then, she underwent a total hysterectomy/bilateral salpingo-oophorectomy. The patient underwent germline gene-panel testing for the detection of mutations in cancer predisposing genes. A truncating mutation in the Fanconi anemia complementation group M (FANCM) gene was detected in heterozygosity, namely, p.Arg658Ter (c.1972C>T, rs368728266). The patient’s family history is unremarkable, with no reported cases of breast or ovarian cancer, a fact that can be attributed to the significant lower penetrance of FANCM mutations. 1. Introduction marker Ca 125, which measured at 91.6 U/ml within a two- month period. A 58-year-old Greek woman presented with abdominal Following that, the patient underwent a total hysterec- distension and discomfort. A CT scan was performed on tomy/bilateral salpingo-oophorectomy on 27/9/2017 and, 12/04/2017 depicting ascites, enlarged pelvic lymph nodes, according to the pathology report, an R1 resection. and mesenteric fat turbidity. An abdominal MRI con- One week after the surgery, the patient presented firmed those findings and revealed intraperitoneal implants acute peritonitis due to anastomotic rupture and was sur- of the mesentery. Tumor marker Ca 125 was measured at gically treated with an ileostomy formation. The patient 339.10 U/ml. remained hospitalized for two months because of postopera- Biopsies were performed on 26/04/2017, and histology tive complications (electrolyte imbalance, infected intra- examination revealed a low-grade adenocarcinoma. Immu- abdominal hematoma). nohistochemistry was positive for WT1, ER, and MOC31 The last imaging test was performed on 12/1/2018 and and negative for p53, calretinin, and D240, suggesting either depicted stable disease, while at the same time, Ca 125 values a serous papillary ovarian carcinoma with peritoneal infiltra- were within a normal range. tion or a primary peritoneal carcinoma. Following the national guidelines for ovarian cancer, The patient was administered cytotoxic chemotherapy the patient underwent germline gene-panel testing for the with the combination of paclitaxel (175 mg/m ) and carbo- detection of germline mutations in 94 cancer predisposing platin (AUC 6), resulting in partial clinical and biochemical genes (Illumina TruSight Cancer panel). While no responses with decreasing ascites formation and tumor BRCA1/2 mutations were found, a truncating mutation 2 Case Reports in Oncological Medicine I:1 I:2 II:1 II:2 II:3 II:4 II:5 II:6 d.~86y d.90y CRC~65y d.80y d.old (stroke) (stroke) d.75-77y No FH info No FH info No FH info III:1 III:2 III:3 III:4 III:5 III:6 III:7 III:8 III:9 III:9 III:11 III:12 III:13 III:14 III:15 III:16 95 91 d.90y Leukemia ~68y d.old d.90y d.80y 90 CRC~70y BrCa (stroke) (d.78y) (heart) (renal failure) 80 d.70y IV:2 IV:3 IV:4 IV:5 IV:6 IV:7 IV:8 IV:9 IV:10 IV:11 IV:12 IV:13 IV:14 IV:15 IV:16 IV:17 IV:18 IV:19 IV:1 OvCa 58y 53 - ~45- d.46y 50 50 47 45 58 (heart) FANCM p.Arg658Ter +/- V:1 V:2 V:3 V:4 V:5 27 27 20 33 24 FANCM p.Arg658Ter +/- Figure 1: Pedigree of the patient carrying the loss-of-function monoallelic FANCM mutation p.Arg658Ter. OvCa: ovarian cancer; CRC: colorectal cancer; BrCa: breast cancer. in the Fanconi anemia complementation group M (FANCM) breast/ovarian cancer predisposition genes. The scarcity of gene was detected in heterozygosity, namely, p.Arg658Ter females on the paternal side should also be taken into (c.1972C>T, rs368728266). account. The 20-year-old daughter of the patient also carries FANCM is one of the nearly 20 genes implicated in the the p.Arg658Ter mutation. This case is the first case of ovar- major DNA repair pathway of interstrand crosslinks through ian cancer with FANCM mutation in Greece. homologous recombination (HR). The major breast and/or ovarian cancer predisposing genes BRCA1 and BRCA2 are also members of this pathway, while biallelic mutations in Conflicts of Interest genes of the HR pathway cause Fanconi anemia (FA), a The authors declare that there is no conflict of interest genetically heterogeneous recessive disorder characterized regarding the publication of this paper. by cytogenetic instability, hypersensitivity to DNA crosslink- ing agents, increased chromosomal breakage, and defective DNA repair [1]. References Monoallelic mutations in FANCM, as well as in other FA/HR genes, have been recently linked to breast cancer pre- [1] I. Catucci, A. Osorio, B. Arver et al., “Individuals with FANCM disposition, conferring an approximately 2-fold increase in biallelic mutations do not develop Fanconi anemia, but show lifetime risk for the disease and showing a stronger correla- risk for breast cancer, chemotherapy toxicity and may display tion with the triple-negative phenotype (OR: 3.75) [2]. These chromosome fragility,” Genetics in Medicine, vol. 20, no. 4, findings identify FANCM as a breast cancer susceptibility pp. 452–457, 2017. gene [3]. Although still preliminary, a role for FANCM as [2] G. Neidhardt, J. Hauke, J. Ramser et al., “Association between an ovarian cancer susceptibility gene has very recently loss-of-function mutations within the FANCM gene and emerged [4]. It has to be noted however that dysfunction early-onset familial breast cancer,” JAMA Oncol, vol. 3, no. 9, of the HR mechanism has been strongly linked with pp. 1245–1248, 2017. breast and ovarian cancer predisposition, even though [3] J. I. Kiiski, L. M. Pelttari, S. Khan et al., “Exome sequencing the exact role of each protein involved remains to be identifies FANCM as a susceptibility gene for triple-negative scrutinized with respect to magnitude risks and possible breast cancer,” Proceedings of the National Academy of Sciences, therapeutic implications. vol. 111, no. 42, pp. 15172–15177, 2014. The patient’s family history (Figure 1) is unremarkable, [4] E. Dicks, H. Song, S. J. Ramus et al., “Germline whole exome with no reported cases of breast or ovarian cancers. This sequencing and large-scale replication identifies FANCM as a however can be attributed to the lower penetrance of likely high grade serous ovarian cancer susceptibility gene,” FANCM mutations, compared to that of the major Oncotarget, vol. 8, no. 31, pp. 50930–50940, 2017. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation

Loading next page...
 
/lp/hindawi-publishing-corporation/a-patient-affected-with-serous-ovarian-peritoneal-carcinoma-carrying-pqFzx7RrVn
Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2019 Adamantia Nikolaidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-6706
eISSN
2090-6714
DOI
10.1155/2019/9357924
Publisher site
See Article on Publisher Site

Abstract

Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 9357924, 2 pages https://doi.org/10.1155/2019/9357924 Case Report A Patient Affected with Serous Ovarian/Peritoneal Carcinoma Carrying the FANCM Mutation 1 2 1 Adamantia Nikolaidi , Irene Konstantopoulou , Nikolaos Pistalmantzian, 2 2 1 Florentia Fostira , Drakoulis Yannoukakos, and Ilias Athanasiadis Oncology Department MITERA Hospital, Athens, Greece Molecular Diagnostics Lab, NCSR “Demokritos”, Athens, Greece Correspondence should be addressed to Adamantia Nikolaidi; mantonikolaidi@gmail.com Received 13 February 2019; Accepted 24 March 2019; Published 16 May 2019 Academic Editor: Jose I. Mayordomo Copyright © 2019 Adamantia Nikolaidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of a 58-year-old female with ovarian cancer. The patient presented with ascites, and the biopsies revealed a low-grade adenocarcinoma, either a serous papillary ovarian cancer with peritoneal implants or a primary peritoneal carcinoma. She received neoadjuvant chemotherapy and after 5 cycles achieved partial response, and then, she underwent a total hysterectomy/bilateral salpingo-oophorectomy. The patient underwent germline gene-panel testing for the detection of mutations in cancer predisposing genes. A truncating mutation in the Fanconi anemia complementation group M (FANCM) gene was detected in heterozygosity, namely, p.Arg658Ter (c.1972C>T, rs368728266). The patient’s family history is unremarkable, with no reported cases of breast or ovarian cancer, a fact that can be attributed to the significant lower penetrance of FANCM mutations. 1. Introduction marker Ca 125, which measured at 91.6 U/ml within a two- month period. A 58-year-old Greek woman presented with abdominal Following that, the patient underwent a total hysterec- distension and discomfort. A CT scan was performed on tomy/bilateral salpingo-oophorectomy on 27/9/2017 and, 12/04/2017 depicting ascites, enlarged pelvic lymph nodes, according to the pathology report, an R1 resection. and mesenteric fat turbidity. An abdominal MRI con- One week after the surgery, the patient presented firmed those findings and revealed intraperitoneal implants acute peritonitis due to anastomotic rupture and was sur- of the mesentery. Tumor marker Ca 125 was measured at gically treated with an ileostomy formation. The patient 339.10 U/ml. remained hospitalized for two months because of postopera- Biopsies were performed on 26/04/2017, and histology tive complications (electrolyte imbalance, infected intra- examination revealed a low-grade adenocarcinoma. Immu- abdominal hematoma). nohistochemistry was positive for WT1, ER, and MOC31 The last imaging test was performed on 12/1/2018 and and negative for p53, calretinin, and D240, suggesting either depicted stable disease, while at the same time, Ca 125 values a serous papillary ovarian carcinoma with peritoneal infiltra- were within a normal range. tion or a primary peritoneal carcinoma. Following the national guidelines for ovarian cancer, The patient was administered cytotoxic chemotherapy the patient underwent germline gene-panel testing for the with the combination of paclitaxel (175 mg/m ) and carbo- detection of germline mutations in 94 cancer predisposing platin (AUC 6), resulting in partial clinical and biochemical genes (Illumina TruSight Cancer panel). While no responses with decreasing ascites formation and tumor BRCA1/2 mutations were found, a truncating mutation 2 Case Reports in Oncological Medicine I:1 I:2 II:1 II:2 II:3 II:4 II:5 II:6 d.~86y d.90y CRC~65y d.80y d.old (stroke) (stroke) d.75-77y No FH info No FH info No FH info III:1 III:2 III:3 III:4 III:5 III:6 III:7 III:8 III:9 III:9 III:11 III:12 III:13 III:14 III:15 III:16 95 91 d.90y Leukemia ~68y d.old d.90y d.80y 90 CRC~70y BrCa (stroke) (d.78y) (heart) (renal failure) 80 d.70y IV:2 IV:3 IV:4 IV:5 IV:6 IV:7 IV:8 IV:9 IV:10 IV:11 IV:12 IV:13 IV:14 IV:15 IV:16 IV:17 IV:18 IV:19 IV:1 OvCa 58y 53 - ~45- d.46y 50 50 47 45 58 (heart) FANCM p.Arg658Ter +/- V:1 V:2 V:3 V:4 V:5 27 27 20 33 24 FANCM p.Arg658Ter +/- Figure 1: Pedigree of the patient carrying the loss-of-function monoallelic FANCM mutation p.Arg658Ter. OvCa: ovarian cancer; CRC: colorectal cancer; BrCa: breast cancer. in the Fanconi anemia complementation group M (FANCM) breast/ovarian cancer predisposition genes. The scarcity of gene was detected in heterozygosity, namely, p.Arg658Ter females on the paternal side should also be taken into (c.1972C>T, rs368728266). account. The 20-year-old daughter of the patient also carries FANCM is one of the nearly 20 genes implicated in the the p.Arg658Ter mutation. This case is the first case of ovar- major DNA repair pathway of interstrand crosslinks through ian cancer with FANCM mutation in Greece. homologous recombination (HR). The major breast and/or ovarian cancer predisposing genes BRCA1 and BRCA2 are also members of this pathway, while biallelic mutations in Conflicts of Interest genes of the HR pathway cause Fanconi anemia (FA), a The authors declare that there is no conflict of interest genetically heterogeneous recessive disorder characterized regarding the publication of this paper. by cytogenetic instability, hypersensitivity to DNA crosslink- ing agents, increased chromosomal breakage, and defective DNA repair [1]. References Monoallelic mutations in FANCM, as well as in other FA/HR genes, have been recently linked to breast cancer pre- [1] I. Catucci, A. Osorio, B. Arver et al., “Individuals with FANCM disposition, conferring an approximately 2-fold increase in biallelic mutations do not develop Fanconi anemia, but show lifetime risk for the disease and showing a stronger correla- risk for breast cancer, chemotherapy toxicity and may display tion with the triple-negative phenotype (OR: 3.75) [2]. These chromosome fragility,” Genetics in Medicine, vol. 20, no. 4, findings identify FANCM as a breast cancer susceptibility pp. 452–457, 2017. gene [3]. Although still preliminary, a role for FANCM as [2] G. Neidhardt, J. Hauke, J. Ramser et al., “Association between an ovarian cancer susceptibility gene has very recently loss-of-function mutations within the FANCM gene and emerged [4]. It has to be noted however that dysfunction early-onset familial breast cancer,” JAMA Oncol, vol. 3, no. 9, of the HR mechanism has been strongly linked with pp. 1245–1248, 2017. breast and ovarian cancer predisposition, even though [3] J. I. Kiiski, L. M. Pelttari, S. Khan et al., “Exome sequencing the exact role of each protein involved remains to be identifies FANCM as a susceptibility gene for triple-negative scrutinized with respect to magnitude risks and possible breast cancer,” Proceedings of the National Academy of Sciences, therapeutic implications. vol. 111, no. 42, pp. 15172–15177, 2014. The patient’s family history (Figure 1) is unremarkable, [4] E. Dicks, H. Song, S. J. Ramus et al., “Germline whole exome with no reported cases of breast or ovarian cancers. This sequencing and large-scale replication identifies FANCM as a however can be attributed to the lower penetrance of likely high grade serous ovarian cancer susceptibility gene,” FANCM mutations, compared to that of the major Oncotarget, vol. 8, no. 31, pp. 50930–50940, 2017. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Journal

Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: May 16, 2019

References