Rare Hereditary Gynecological Cancer Syndromes

Watanabe, Takafumi; Soeda, Shu; Endo, Yuta; Okabe, Chikako; Sato, Tetsu; Kamo, Norihito; Ueda, Makiko; Kojima, Masayasu; Furukawa, Shigenori; Nishigori, Hidekazu; Takahashi, Toshifumi; Fujimori, Keiya

doi:10.3390/ijms23031563

Cited by 6 publications

(11 citation statements)

References 145 publications

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“…Hereditary cancers carry unique significance as they tend to develop earlier and confer a heightened risk of aggressive, multifocal, and bilateral cancers [12]. About 5-10% of malignancies result from hereditary predisposition syndromes, highlighting their substantial impact [13,14]. These syndromes, often stemming from mutations in key genes involved in cell regulation and DNA repair, elevate cancer risk, as exemplified by CS and PTEN mutations [15].…”

Section: Pathophysiology Of the Phtsmentioning

confidence: 99%

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

Pîrlog,

Pătrășcanu,

Militaru

et al. 2024

Medicina

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PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.

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Section: Pathophysiology Of the Phtsmentioning

confidence: 99%

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

Pîrlog,

Pătrășcanu,

Militaru

et al. 2024

Medicina

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“…HBOC is known to have a higher incidence of OC, and LS is known to have higher incidences of endometrial cancer (EC) and OC. Other rarer gynecological related hereditary syndromes include Cowden syndrome (CS), Peutz‐Jeghers syndrome (PJS), DICER1 syndrome, rhabdoid tumor predisposition syndrome (RTPS) 2, and Li–Fraumeni syndrome (LFS) 13 …”

Section: Introductionmentioning

confidence: 99%

“…Other rarer gynecological related hereditary syndromes include Cowden syndrome (CS), Peutz-Jeghers syndrome (PJS), DICER1 syndrome, rhabdoid tumor predisposition syndrome (RTPS) 2, and Li-Fraumeni syndrome (LFS). 13 In the present manuscript, we discuss the relationship between clinicopathological features and somatic mutated genes that are commonly detected in gynecological cancers, such as PIK3CA, TP53, KRAS, PTEN, CTNNB1, ARID1A, and FBXW7 (Table 1). Next, we describe the characteristics and clinical management of inherited cancer syndromes caused by GPVs in gynecological cancer susceptibility genes, including BRCA1/2, MMR, PTEN, STK11, DICER1, SMARCA4, and TP53 (Table 2).…”

Section: Introductionmentioning

confidence: 99%

Landscape of somatic mutated genes and inherited susceptibility genes in gynecological cancer

Watanabe,

Soeda,

Okoshi

et al. 2023

J of Obstet and Gynaecol

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Traditionally, gynecological cancers have been classified based on histology. Since remarkable advancements in next‐generation sequencing technology have enabled the exploration of somatic mutations in various cancer types, comprehensive sequencing efforts have revealed the genomic landscapes of some common forms of human cancer. The genomic features of various gynecological malignancies have been reported by several studies of large‐scale genomic cohorts, including The Cancer Genome Atlas. Although recent comprehensive genomic profiling tests, which can detect hundreds of genetic mutations at a time from cancer tissues or blood samples, have been increasingly used as diagnostic clinical biomarkers and in therapeutic management decisions, germline pathogenic variants associated with hereditary cancers can also be detected using this test. Gynecological cancers are closely related to genetic factors, with approximately 5% of endometrial cancer cases and 20% of ovarian cancer cases being caused by germline pathogenic variants. Hereditary breast and ovarian cancer syndrome and Lynch syndrome are the two major cancer susceptibility syndromes among gynecological cancers. In addition, several other hereditary syndromes have been reported to be associated with gynecological cancers. In this review, we highlight the genes for somatic mutation and germline pathogenic variants commonly seen in gynecological cancers. We first describe the relationship between clinicopathological attributes and somatic mutated genes. Subsequently, we discuss the characteristics and clinical management of inherited cancer syndromes resulting from pathogenic germline variants in gynecological malignancies.

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“…LS is related to pathogenic germline variants in DNA mismatch repair (MMR) genes ( MLH1 , MSH2 , MSH6 , PMS2 ) or EPCAM and [ 8 , 9 ]. Of note, many patients that fulfill the criteria of hereditary cancer predisposition syndromes do not exhibit pathogenic variants in the main genes described as altered in these syndromes [ 4 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Co-Occurrence of Germline Genomic Variants and Copy Number Variations in Hereditary Breast and Colorectal Cancer Patients

Cortes

Basso²,

Villacis

et al. 2023

Genes

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Hereditary Breast and Ovarian Cancer (HBOC) syndrome is an autosomal dominant disease associated with a high risk of developing breast, ovarian, and other malignancies. Lynch syndrome is caused by mutations in mismatch repair genes predisposing to colorectal and endometrial cancers, among others. A rare phenotype overlapping hereditary colorectal and breast cancer syndromes is poorly characterized. Three breast and colorectal cancer unrelated patients fulfilling clinical criteria for HBOC were tested by whole exome sequencing. A family history of colorectal cancer was reported in two patients (cases 2 and 3). Several variants and copy number variations were identified, which potentially contribute to the cancer risk or prognosis. All patients presented copy number imbalances encompassing PMS2 (two deletions and one duplication), a known gene involved in the DNA mismatch repair pathway. Two patients showed gains covering the POLE2 (cases 1 and 3), which is associated with DNA replication. Germline potentially damaging variants were found in PTCH1 (patient 3), MAT1A, and WRN (patient 2). Overall, concurrent genomic alterations were described that may increase the risk of cancer appearance in HBOC patients with breast and colorectal cancers.

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Rare Hereditary Gynecological Cancer Syndromes

Cited by 6 publications

References 145 publications

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

Landscape of somatic mutated genes and inherited susceptibility genes in gynecological cancer

Co-Occurrence of Germline Genomic Variants and Copy Number Variations in Hereditary Breast and Colorectal Cancer Patients

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