Jacek Gronwald,
Jacek Gronwald
Institution: NULL
Email:
Cezary Cybulski,
Cezary Cybulski
Institution: NULL
Email:
Tomasz Huzarski,
Tomasz Huzarski
Institution: NULL
Email:
Anna Jakubowska,
Anna Jakubowska
Institution: NULL
Email:
Tadeusz Debniak,
Tadeusz Debniak
Institution: NULL
Email:
Marcin Lener,
Marcin Lener
Institution: NULL
Email:
Steven A Narod,
Steven A Narod
Institution: NULL
Email:
Jan Lubinski
Jan Lubinski
Institution: NULL
Email:
BRCA1 and BRCA2 mutations contribute to both breast cancer and ovarian cancer worldwide. In Poland approximately 4% of patients with breast cancers and 10% of patients with ovarian cancer carry a mutation in BRCA1. The majority of mutations consist of three founder mutations. A rapid inexpensive tes...
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BRCA1 and BRCA2 mutations contribute to both breast cancer and ovarian cancer worldwide. In Poland approximately 4% of patients with breast cancers and 10% of patients with ovarian cancer carry a mutation in BRCA1. The majority of mutations consist of three founder mutations. A rapid inexpensive test for these three mutations can be used to screen all Polish adults at a reasonable cost. In the region of Pomerania of North-western Poland nearly half a million tests have been performed, in large part through engaging family doctors and providing ready access to testing through the Pomeranian Medical University. The following commentary provides a history of genetic testing for cancer in Pomerania and the current approach to facilitating access to genetic testing at the Cancer Family Clinic for all adults living in the region.
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Posted 1 week ago
Ichiro Tsuboi,
Ichiro Tsuboi
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Momoko Araki,
Momoko Araki
Institution: Shimane University Faculty of Medicine Department of Clinical Genetics Unit, , Izumo, Japan
Email:
Shuhei Yokoyama,
Shuhei Yokoyama
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Gen Tanaka,
Gen Tanaka
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Kazutaka Mitani,
Kazutaka Mitani
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Saori Yosioka,
Saori Yosioka
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Yusuke Kobayashi,
Yusuke Kobayashi
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Hirochika Nakajima,
Hirochika Nakajima
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Taichi Nagami,
Taichi Nagami
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Kohei Ogawa,
Kohei Ogawa
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Chiaki Koike,
Chiaki Koike
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Koichiro Wada
Koichiro Wada
Institution: Shimane University Faculty of Medicine Department of Urology, , Izumo, Japan
Email:
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal ce...
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal cell carcinoma (RCC). HLRCC-associated RCC is aggressive and diagnosed at a much earlier age than sporadic RCC. It is essential for carriers of HLRCC to undergo annual renal screening by magnetic resonance imaging to detect early stage RCCs. Metastatic HLRCC-associated RCC must be treated by systemic therapy; however, it is unclear which medicines are most effective in treating this cancer owing to its low incidence rate. Immune checkpoint inhibitor (ICI) combinations or ICIs plus tyrosine kinase inhibitors are administered as systemic therapy for clear cell RCC. Here, we report a patient with HLRCC-associated RCC treated with sequential therapy, including ipilimumab plus nivolumab combination and cabozantinib, after diagnosis of HLRCC-associated RCC using FoundationOne Liquid CDx and single-site analysis. We also investigated familial FH mutations and describe a new family pedigree for HLRCC.
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Posted 1 week ago
Akihiro Ohmoto,
Akihiro Ohmoto
Institution: NULL
Email:
Naomi Hayashi,
Naomi Hayashi
Institution: NULL
Email:
Shunji Takahashi,
Shunji Takahashi
Institution: NULL
Email:
Arisa Ueki
Arisa Ueki
Institution: NULL
Email:
Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent stu...
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Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germline TP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazilian is known as low penetrant. While 50–80% of pediatric ACC patients harbored a LFS, such a strong causal relationship is not observed in adult patients, which suggests different pathophysiologies between the two populations. As for PPGL, because multiple driver genes, such as succinate dehydrogenase (SDH)-related genes, RET, NF1, and VHL have been identified, universal multi-gene germline panel testing is warranted as a comprehensive and cost-effective approach. PPGL pathogenesis is divided into three molecular pathways (pseudohypoxia, Wnt signaling, and kinase signaling), and this classification is expected to result in personalized medicine based on genomic profiles. It remains unknown whether clinical characteristics differ between cases derived from genetic predisposition syndromes and sporadic cases, or whether the surveillance strategy should be changed depending on the genetic background or whether it should be uniform. Close cooperation among medical genomics experts, endocrinologists, oncologists, and early investigators is indispensable for improving the clinical management for multifaceted ACC and PPGL.
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Posted 1 week ago
Maneesh Singh
Maneesh Singh
Institution: Kansas City university
Email:
The purpose of this paper is to provide a review of hereditary non-polyposis colorectal cancer. This paper covers the causes, epidemiology, pathophysiology, histology, diagnosis, and treatment for the disease.
Posted 1 week ago
Annmarie Taheny,
Annmarie Taheny
Institution: NULL
Email:
Haylie McSwaney,
Haylie McSwaney
Institution: NULL
Email:
Julia Meade
Julia Meade
Institution: NULL
Email:
Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagn...
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Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient’s family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient’s screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.
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Posted 1 week ago
Fangfang Gao,
Fangfang Gao
Institution: NULL
Email:
Dejian Gu,
Dejian Gu
Institution: NULL
Email:
He Zhang,
He Zhang
Institution: NULL
Email:
Chao Shi,
Chao Shi
Institution: NULL
Email:
Feng Du,
Feng Du
Institution: NULL
Email:
Bo Zheng,
Bo Zheng
Institution: NULL
Email:
Huijuan Wu,
Huijuan Wu
Institution: NULL
Email:
Yanqiu Zhao
Yanqiu Zhao
Institution: NULL
Email:
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have...
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.
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Posted 1 week ago
Yue Yin Xia,
Yue Yin Xia
Institution: NULL
Email:
Joanne Kotsopoulos
Joanne Kotsopoulos
Institution: NULL
Email:
BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over ti...
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BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over time have introduced lower hormonal dosages, different steroid types and non-oral routes of administration. Specifically, there has been a considerable shift in patterns of contraceptive use and the increase in the uptake of non-oral, long-acting, reversible contraception (e.g., intrauterine devices, implants, injections) has corresponded to a decline in oral contraceptive pill use. Whether or not these other methods confer a protective effect against ovarian cancer in the general population is not clear. To our knowledge, there have been no such studies conducted among BRCA mutation carriers. Furthermore, the impact of these changes on the risk of developing ovarian cancer is not known. In this article, we will review the existing epidemiologic evidence regarding the role of contraceptives and the risk of ovarian cancer with a focus on women with a BRCA1 or BRCA2 mutation. We will discuss recent findings and gaps in the knowledge while extrapolating from studies conducted among women from the noncarrier population.
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Posted 1 week ago
Tina Kamani,
Tina Kamani
Institution: NULL
Email:
Parsa Charkhchi,
Parsa Charkhchi
Institution: NULL
Email:
Afshan Zahedi,
Afshan Zahedi
Institution: NULL
Email:
Mohammad R. Akbari
Mohammad R. Akbari
Institution: NULL
Email:
Non-medullary thyroid cancer (NMTC) is the most common type of thyroid cancer. With the increasing incidence of NMTC in recent years, the familial form of the disease has also become more common than previously reported, accounting for 5–15% of NMTC cases. Familial NMTC is further classified as no...
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Non-medullary thyroid cancer (NMTC) is the most common type of thyroid cancer. With the increasing incidence of NMTC in recent years, the familial form of the disease has also become more common than previously reported, accounting for 5–15% of NMTC cases. Familial NMTC is further classified as non-syndromic and the less common syndromic FNMTC. Although syndromic NMTC has well-known genetic risk factors, the gene(s) responsible for the vast majority of non-syndromic FNMTC cases are yet to be identified. To date, several candidate genes have been identified as susceptibility genes in hereditary NMTC. This review summarizes genetic predisposition to non-medullary thyroid cancer and expands on the role of genetic variants in thyroid cancer tumorigenesis and the level of penetrance of NMTC-susceptibility genes.
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Posted 1 week ago
Sophie Ferlicot,
Sophie Ferlicot
Institution: NULL
Email:
Pierre-Alexandre Just,
Pierre-Alexandre Just
Institution: NULL
Email:
Eva Compérat,
Eva Compérat
Institution: NULL
Email:
Etienne Rouleau,
Etienne Rouleau
Institution: NULL
Email:
Frédérique Tissier,
Frédérique Tissier
Institution: NULL
Email:
Christophe Vaessen,
Christophe Vaessen
Institution: NULL
Email:
Stéphane Richard
Stéphane Richard
Institution: NULL
Email:
Background
Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, dis...
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Background
Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome.
Case presentation
We describe the case of a 51-year-old man with a germline MET mutation detected on peripheral blood testing, and no germline VHL mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed 7 years after the initial diagnosis corresponding to a clear cell RCC metastasis. By immunohistochemistry, clear cell tumors showed focal cytokeratin 7, moderate racemase, and diffuse and membranous CAIX expression, while papillary tumors expressed strong diffuse cytokeratin 7 and racemase without CAIX positivity. Using FISH, VHL deletion was observed in one of the clear cell tumors, and the metastatic clear cell tumor presented a trisomy of chromosomes 7 and 17. These last genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome.
Conclusions
The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.
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Posted 1 week ago
Karel Mercken,
Karel Mercken
Institution: NULL
Email:
Brecht Van Berkel,
Brecht Van Berkel
Institution: NULL
Email:
Liesbeth De Wever
Liesbeth De Wever
Institution: NULL
Email:
In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase–deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical fo...
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In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase–deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical for diagnosis and management.
Teaching point: When a renal lesion suspected of RCC is identified in a patient with cutaneous and uterine leiomyomas, HLRCC should be evaluated, which is important for future genetic counseling.
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