Abstract：
:Germ-line mutations in the tumour suppressor genes BRCA1 and BRCA2 predispose to breast and ovarian cancer. Since 1999 we have performed mutational screening of breast and/or ovarian cancer patients in East Denmark. During this period we have identified 40 novel sequence variations in BRCA1 and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1 synonymous variant. The remaining 24 variants were identified in BRCA2, including 10 deleterious mutants (6 frame-shift and 4 nonsense), 2 intronic variants, 10 missense mutations and 2 synonymous variants. The frequency of the variants of unknown significance was examined in control individuals. Moreover, the presumed significance of the missense mutations was predicted in silico using the align GVGD algorithm. In conclusion, the mutation screening identified 40 novel variants in the BRCA1 and BRCA2 genes and thereby extends the knowledge of the BRCA1/BRCA2 mutation spectrum. Nineteen of the mutations were interpreted as pathogenic, 3 missense mutations were suggested to be pathogenic based on in silico analysis, 6 mutations were suggested to be benign since they were identified in patients together with a well-known disease-causing BRCA1/BRCA2 mutation, while 12 were variants of unknown significance.
journal_name
Fam Cancerjournal_title
Familial cancerauthors
Hansen TV,Jønson L,Steffensen AY,Andersen MK,Kjaergaard S,Gerdes AM,Ejlertsen B,Nielsen FCdoi
10.1007/s10689-011-9422-5subject
Has Abstractpub_date
2011-06-01 00:00:00pages
207-12issue
2eissn
1389-9600issn
1573-7292journal_volume
10pub_type
杂志文章相关文献
Familial Cancer文献大全abstract：:The identification of germline pathogenic/likely pathogenic (P/LP) variants in cancer predisposition genes can guide treatment and management decisions for the individual being tested and potentially at-risk relatives. Prior studies have raised concerns of racial/ethnic disparities in the detection rates of P/LP varia...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-019-00144-6
更新日期：2019-10-01 00:00:00
abstract：:PTCH1 and SUFU are both regulators of the sonic hedgehog signalling pathway. Germline inactivating mutations in both genes are associated with multisystem phenotypes including medulloblastoma. Somatic inactivating mutations in PTCH1 and SUFU each occur in approximately 10% of medulloblastomas. Recently, SUFU mutations...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-010-9411-0
更新日期：2011-06-01 00:00:00
abstract：:Genomic rearrangement occasionally affects the BRCA1/2 genes in Caucasian breast cancer patients. However, the incidence of BRCA1/2 genomic rearrangement in Asians, including the Korean population, has not been well established. Here, we investigated the contribution of BRCA1/2 genomic rearrangement to high-risk breas...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9279-z
更新日期：2009-01-01 00:00:00
abstract：:Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS. We present a famil...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-006-9115-7
更新日期：2007-01-01 00:00:00
abstract：:While a dominant inheritance of breast cancer (vertical inheritance) is well known, less is known about a possible recessive inheritance (horizontal inheritance). In a clinical series of 1676 breast cancer patient's family history was scored as vertical (grandmother-aunt-mother-sister-daughter) or horizontal (sister-s...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-010-9355-4
更新日期：2010-12-01 00:00:00
abstract：:The initial enthusiasm generated by the discovery of the first susceptibility gene found for melanoma has slightly dampened over recent years. For the majority of melanoma families the underlying gene defect is still not known, so the search for other melanoma genes is continuing. Also, the increased risk of melanoma ...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1023/a:1025758527675
更新日期：2003-01-01 00:00:00
abstract：:Peutz-Jeghers syndrome (PJS) is a hereditary polyposis syndrome characterized by hamartomatous Peutz-Jeghers polyps in the gastrointestinal tract, mucocutaneous pigmentations, and increased risk for intestinal and extraintestinal cancer. In more than two-third of patients it is possible to detect pathogenic variants i...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-020-00191-4
更新日期：2020-06-06 00:00:00
abstract：:The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called "deficient MMR" phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigeneti...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-0032-8
更新日期：2018-04-01 00:00:00
abstract：:This article is based upon a literature overview of cancer in Jews. It involves a comparison of variation in incidence and prevalence rates between Jews and non-Jews. However, the reader must exercise a certain amount of skepticism when considering secular changes in cancer incidence and prevalence and the public heal...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-004-9538-y
更新日期：2004-01-01 00:00:00
abstract：:Lynch syndrome is the most frequent hereditary colorectal cancer (CRC) syndrome, affecting approximately 1 in 300 in the Western population. It is caused by pathogenic variants in the mismatch repair (MMR) genes including MLH1, MSH2 (EPCAM), MSH6 and PMS2, and is associated with high risks of CRC, endometrial cancer a...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-020-00225-x
更新日期：2021-01-19 00:00:00
abstract：:To support persons having a genetic predisposition to cancer and their partners during reproductive decision-making, an online decision aid was developed and evaluated. To maximize the impact of the support tool, this mixed methods study aims at developing the optimal implementation strategy for the decision aid. A qu...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-019-00119-7
更新日期：2019-04-01 00:00:00
abstract：OBJECTIVE:To determine the indications, patterns of practice, and complication rates for prophylactic oophorectomy in Ontario. METHODS:From hospital discharge abstracts, 82 hospitals were identified where at least one patient had a prophylactic oophorectomy since 1992. Ethics approval for the chart review was obtained...
journal_title：Familial cancer
pub_type： 杂志文章,多中心研究
doi：10.1023/a:1021174604905
更新日期：2001-01-01 00:00:00
abstract：:Pheochromocytoma is a tumor that originates from the adrenal cortex and sympathetic chains. Most pheochromocytomas are sporadic, whereas others occur as hereditary syndromes. Familial pheochromocytoma has been frequently found in association with various mutations in genes of the succinate dehydrogenase family. A 21-y...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-010-9359-0
更新日期：2010-12-01 00:00:00
abstract：:Through germline multigene panel testing, we discovered the co-occurrence of Lynch syndrome due to a PMS2 mutation and juvenile polyposis syndrome due to a BMPR1A mutation in a young man with synchronous bladder and colorectal cancers and a family history of colorectal polyps. To our knowledge, this is the first repor...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-0012-z
更新日期：2018-01-01 00:00:00
abstract：:Family history of breast cancer is a key risk factor, accounting for up to 10% of cancers. We evaluated the proactive assessment of familial breast cancer (FBC) risk in primary care. Eligible women (30 to 60 years) were recruited from eight English general practices. Practices were trained on FBC risk assessment. In f...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-020-00188-z
更新日期：2020-06-11 00:00:00
abstract：:Neurofibromatosis type 2 (NF2) is associated with the development of several types of benign nervous system tumours, while malignancies are rare. We report a 22-year-old man who presented with retroperitoneal and spinal high-grade sarcomas with epithelial features. Samples showed a mixed epithelioid and spindled cell ...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-018-0084-4
更新日期：2019-01-01 00:00:00
abstract：:Germline p53 mutations are associated with Li-Fraumeni syndrome (LFS) and other familial cancer phenotypes not fulfilling the definition for LFS. The majority of germline p53 mutations cluster in exons 5-8, corresponding to a DNA binding domain. We report the identification of two germline mutations and a somatic muta...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9284-2
更新日期：2009-01-01 00:00:00
abstract：:One of a pair of monozygous twins was diagnosed and died of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) at the age of 30 years. Her sister remained unaffected and was very concerned about her risk for developing SCCOHT. By performing comprehensive molecular analysis using whole exome sequencing (W...
journal_title：Familial cancer
pub_type： 信件
doi：10.1007/s10689-018-0108-0
更新日期：2019-04-01 00:00:00
abstract：:To optimally inform counselees about their and their relatives' risks, information about lifestyle risk factors, e.g. physical activity and alcohol consumption, might be discussed in breast cancer genetic counselling. This study explored whether lifestyle was discussed, on whose initiative, whether information and/or ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-013-9672-5
更新日期：2014-03-01 00:00:00
abstract：:Following the identification in a proband of a germline BRCA1/BRCA2 mutation in hereditary breast-ovarian cancer (HBOC) or a DNA mismatch repair gene mutation in Lynch syndrome (LS) he or she will be asked to inform at-risk family members about the option for presymptomatic DNA testing. However, in clinical practice m...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-018-0089-z
更新日期：2019-01-01 00:00:00
abstract：:Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-9982-0
更新日期：2017-10-01 00:00:00
abstract：:In the absence of a polyposis phenotype, colorectal cancer (CRC) patients referred for genetic testing because of early-onset disease and/or a positive family history, typically undergo testing for molecular signs of Lynch syndrome in their tumors. In the absence of these signs, DNA testing for germline mutations asso...
journal_title：Familial cancer
pub_type： 杂志文章,评审
doi：10.1007/s10689-012-9570-2
更新日期：2013-03-01 00:00:00
abstract：:Medulloblastoma tumours may arise sporadically or as part of an inherited syndrome. A subset of children with medulloblastoma carry germline and somatic mutations in the SUFU tumour suppressor gene located at 10q24. We report a 55 year old woman referred for investigation on the basis of skin lesions and a family hist...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-014-9752-1
更新日期：2015-03-01 00:00:00
abstract：:Biallelic pathogenic variants (PVs) in MUTYH cause MUTYH-Associated Polyposis (MAP), which displays phenotypic overlap with other hereditary colorectal cancer (CRC) syndromes including Familial Adenomatous Polyposis (FAP) and Lynch syndrome. We report the phenotypic spectrum of MAP in the context of multi-gene heredit...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-018-00116-2
更新日期：2019-04-01 00:00:00
abstract：:The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of "other cancers" in 268 BRCA1 families and 222 BRCA...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-011-9506-2
更新日期：2012-06-01 00:00:00
abstract：:Germline CDH1 mutation carriers are at risk for early-onset diffuse gastric cancer (DGC) and female carriers have an additional risk of lobular breast cancer. The reported literature GC risk of 70% has led to the recommendation for germline mutation carriers to undergo prophylactic total gastrectomy (PTG). The objecti...
journal_title：Familial cancer
pub_type： 杂志文章,多中心研究
doi：10.1007/s10689-019-00133-9
更新日期：2019-10-01 00:00:00
abstract：:We report on three brothers affected by pancreatic tumors, all due to different causes, including mutations associated with two different cancer predisposition syndromes in the same individual. In the index patient a germline mutation both in the APC and BRCA2 gene was identified while one affected brother showed the ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-016-9952-y
更新日期：2017-04-01 00:00:00
abstract：:Colorectal cancer (CRC) risk associated with germline monoallelic MUTYH mutations remains controversial, although a slightly increased risk for this disease has been suggested. MUTYH and MSH6 proteins act in cooperation during the DNA repair process. Based on this interaction, it was hypothesized that the combination ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-009-9282-4
更新日期：2009-01-01 00:00:00
abstract：:Cowden syndrome (CS) is a cancer predisposition syndrome caused by germline mutations in the PTEN tumor suppressor gene. It is associated with an increased risk of thyroid, breast and endometrial cancer but many manifestations can be found in the head and neck region, some of which are pathognomonic. Here we report a ...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-011-9472-8
更新日期：2011-12-01 00:00:00
abstract：:Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and P...
journal_title：Familial cancer
pub_type： 杂志文章
doi：10.1007/s10689-017-0039-1
更新日期：2018-07-01 00:00:00
