Nuclear Pedigree Criteria of Suspected HNPCC

Kładny, Józef; Möslein, Gabriela; Myrhøj, T; Kurzawski, Grzegorz; Jakubowska, Anna; Dębniak, Tadeusz; Petriczko, Wojciech; Kozłowski, Michał; Al-Amawi, Tariq; Brzosko, Marek; Fliciński, Jacek; Jawień, Arkadiusz; Banaszkiewicz, Zbigniew; Rychter, Piotr; Lubiński, Jan

doi:10.1186/1897-4287-1-1-34

Cited by 10 publications

(6 citation statements)

References 17 publications

(13 reference statements)

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“…Two hundred and twenty‐six unrelated patients affected by colorectal cancer or an HNPCC‐associated cancer (endometrium, small bowel, urinary tract) were from families matching the Amsterdam II criteria or at least our modified criteria of suspected HNPCC – one colorectal cancer patient with at least one first‐degree relative affected by colorectal cancer or other HNPCC associated cancers, where at least one of family members was diagnosed under the age of 50 years (24). The clinical diagnosis of HNPCC was established or verified at the International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.…”

Section: Methodsmentioning

confidence: 99%

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)

et al. 2005

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Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 families with MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at least twice in our own series. Two of the most frequent alterations were a substitution of A to T at the splice donor site of intron 5 of MSH2 and a missense change (A681T) of MLH1 found in 10 and eight families, respectively. Among large deletions detected by the multiplex ligation-dependent probe amplification assay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screening protocol specific for the Polish population that is limited to the detection of all reported mutations will result in the identification of the majority of changes present in MLH1 and MSH2 genes in Polish HNPCC kindreds.

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Section: Methodsmentioning

confidence: 99%

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)

et al. 2005

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“…The Amsterdam criteria [ 28 ] and the more recent Amsterdam II criteria, [ 29 ] as well as the Bethesda [ 30 ] (Table 3 ) or European experts' [ 31 , 32 ] guidelines are clinically useful in the diagnosis of HNPCC. However useful these criteria might be for assessing the diagnosis of HNPCC, there will be clinical situations wherein the family may be uninformative for their application, such as it often occurs in very small families.…”

Section: What Is Hnpcc (Lynch Syndrome)?mentioning

confidence: 99%

HNPCC (Lynch Syndrome): Differential Diagnosis, Molecular Genetics and Management - a Review

Lynch

Lynch²,

Shaw³

et al. 2003

Hered Cancer Clin Pract

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HNPCC (Lynch syndrome) is the most common form of hereditary colorectal cancer (CRC), wherein it accounts for between 2-7 percent of the total CRC burden. When considering the large number of extracolonic cancers integral to the syndrome, namely carcinoma of the endometrium, ovary, stomach, hepatobiliary system, pancreas, small bowel, brain tumors, and upper uroepithelial tract, these estimates of its frequency are likely to be conservative. The diagnosis is based upon its natural history in concert with a comprehensive cancer family history inclusive of all anatomic sites. In order for surveillance and management to be effective and, indeed, lifesaving, among these high-risk patients, the linchpin to cancer control would be the physician, who must be knowledgeable about hereditary cancer syndromes, their molecular and medical genetics, genetic counseling, and, most importantly, the natural history of the disorders, so that the entirety of this knowledge can be melded to highly-targeted management.

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“…The second group consisted of 468 unrelated patients from families meeting our LS diagnostic criteria (at least 2 CRCs or CRC and LS‐related cancer, eg, endometrial, ovarian <50 years, small bowel, urinary tract; cancers were diagnosed in 1° degree relatives (or in the same patient); at least 1 cancer was diagnosed under age of 50; and Familial adenomatous polyposis (FAP) was excluded) . A total of 352 families were CRCs‐only.…”

Section: Methodsmentioning

confidence: 99%

New EPCAM founder deletion in Polish population

et al. 2017

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It is well known that founder mutations associated with cancer risk have useful implications for molecular diagnostics. We report the presence of a founder mutation in EPCAM involved in the etiology of Lynch syndrome (LS). The mutation extends nearly 8.7 kb (c.858 + 2478_*4507del) and is shared by 8 Polish families. Family members suffered almost exclusively from colorectal cancer; however, pancreatic and gastric cancers were also apparent. Next to mutations c. 2041G>A in MLH1 gene and c.942+3A>T in MSH2, the deletion mutation encompassing EPCAM is one of the most common causative changes responsible for LS in Poland.

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Nuclear Pedigree Criteria of Suspected HNPCC

Cited by 10 publications

References 17 publications

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)

HNPCC (Lynch Syndrome): Differential Diagnosis, Molecular Genetics and Management - a Review

New EPCAM founder deletion in Polish population

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