Lynch syndrome mutations shared by the Baltic States and Poland

Dymerska, Dagmara; Kurzawski, Grzegorz; Suchy, Janina; Roomere, Hanno; Toome, Kadri; Metspalu, Andres; Janavičius, Ramūnas; Elsakov, Pavel; Irmejs, Arvids; Berzina, Dace; Miklaševičs, Edvīns; Gardovskis, Jānis; Rebane, Egle; Kelve, Merike; Kładny, Józef; Huzarski, Tomasz; Gronwald, Jacek; Dębniak, Tadeusz; Byrski, Tomasz; Stembalska, Agnieszka; Surdyka, Dariusz; Siołek, Monika; Szwiec, Marek; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Kilar, Ewa; Scott, Rodney J.; Lubiński, Jan

doi:10.1111/cge.12251

Cited by 5 publications

(5 citation statements)

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“…This mutation has been reported before in single families from Hungary, Canada and Germany; however, it was not until now considered to be a founder mutation. We were unable to the mutation c. 2041G > A in MLH1 found in 9 families and the c.942 + 3A > T in MSH2 found in 14 families in the previous study, 26 the EPCAM deletion reported herein is one of the most common mutations responsible for LS in Poland. [15][16][17][18]20 We confirmed our founder variant by microarray analysis since 5 of 5 unrelated families shared a common haplotype.…”

Section: Discussioncontrasting

confidence: 70%

“…In summary, 8 Polish families carry the founder variant c.858 + 2478_*4507del in EPCAM . It should be highlighted that next to the mutation c. 2041G > A in MLH1 found in 9 families and the c.942 + 3A > T in MSH2 found in 14 families in the previous study, the EPCAM deletion reported herein is one of the most common mutations responsible for LS in Poland.…”

Section: Discussionmentioning

confidence: 51%

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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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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 51%

New EPCAM founder deletion in Polish population

et al. 2017

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“…The pathogenic MLH1 variant, c.2041G > A, was detected in two unrelated suspected-HNPCC or non-HNPCC families of Punjabi and Urdu-speaking background, respectively. This variant was first reported in Poland as a potential founder variant [4, 31], has been reported as a recurrent variant in Scotland [30] and has also been described once each in Germany [33], and Colombia [3]. These recurrent variants accounted for 58.3% (7/12) of all MLH1/MSH2 carriers from Pakistan.…”

Section: Discussionmentioning

confidence: 98%

“…Our data support the notion that the suspected-HNPCC criteria may be useful for the identification of Pakistani families. The suspected-HNPCC criteria have also been utilized in other studies from Turkey, Poland, Italy and Latvia [31, 32, 37, 46].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients

Rashid

Muhammad

Loya

et al. 2019

Hered Cancer Clin Pract

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BackgroundPathogenic germline variants in MLH1, MSH2 and MSH6 genes account for the majority of Lynch syndrome (LS). In this first report from Pakistan, we investigated the prevalence of pathogenic MLH1/MSH2/MSH6 variants in colorectal cancer (CRC) patients.MethodsConsecutive cases (n = 212) were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), between November 2007 to March 2011. Patients with a family history of > 3 or 2 HNPCC-associated cancers were classified as HNPCC (n = 9) or suspected-HNPCC (n = 20), respectively (group 1; n = 29). Cases with no family history were designated as non-HNPCC (group 2; n = 183). MLH1/MSH2/MSH6 genes were comprehensively screened in group 1. Pathogenic/likely pathogenic variants identified in group 1 were subsequently evaluated in group 2.ResultsEight distinct pathogenic/likely pathogenic MLH1/MSH2 variants were found in group 1 (10/29; 34.5%), belonging to HNPCC (5/9; 55.6%) and suspected-HNPCC (5/20; 25%) families and in group 2 (2/183; 1.1%) belonging to non-HNPCC. Overall, three recurrent variants (MSH2 c.943-1G > C, MLH1 c.1358dup and c.2041G > A) accounted for 58.3% (7/12) of all families harboring pathogenic/likely pathogenic MLH1/MSH2 variants. Pathogenic MSH6 variants were not detected.ConclusionPathogenic/likely pathogenic MLH1/MSH2 variants account for a substantial proportion of CRC patients with HNPCC/suspected-HNPCC in Pakistan. Our findings suggest that HNPCC/suspected-HNPCC families should be tested for these recurrent variants prior to comprehensive gene screening in this population.

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“…c.858 + 2478_*4507del) that was found in the Polish population [ 34 ] may occur in a comparable number to MLH1 (e.g., c. 2041G > A) and MSH2 (e.g. c.942 + 3A > T) mutations [ 35 ]. LS may be suspected by meeting the Amsterdam I or less strict Amsterdam II criteria and the Bethesda guidelines, but currently the diagnosis must be confirmed by a detection germline mutations or deletions [ 36 ].…”

Section: Genetic Syndromes Associated With Hpcmentioning

confidence: 99%

Current status of inherited pancreatic cancer

Bułdak

2022

Hered Cancer Clin Pract

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Background It is estimated that about 10% of pancreatic cancer cases have a genetic background. People with a familial predisposition to pancreatic cancer can be divided into 2 groups. The first is termed hereditary pancreatic cancer, which occurs in individuals with a known hereditary cancer syndrome caused by germline single gene mutations (e.g., BRCA1/2, CDKN2A). The second is considered as familial pancreatic cancer, which is associated with several genetic factors responsible for the more common development of pancreatic cancer in certain families, but the precise single gene mutation has not been found. Aim This review summarizes the current state of knowledge regarding the risk of pancreatic cancer development in hereditary pancreatic cancer and familial pancreatic cancer patients. Furthermore, it gathers the latest recommendations from the three major organizations dealing with the prevention of pancreatic cancer in high-risk groups and explores recent guidelines of scientific societies on screening for pancreatic cancers in individuals at risk for hereditary or familial pancreatic cancer. Conclusions In order to improve patients’ outcomes, authors of current guidelines recommend early and intensive screening in patients with pancreatic cancer resulting from genetic background. The screening should be performed in excellence centers. The scope, extent and cost-effectiveness of such interventions requires further studies.

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Lynch syndrome mutations shared by the Baltic States and Poland

Cited by 5 publications

References 5 publications

New EPCAM founder deletion in Polish population

New EPCAM founder deletion in Polish population

Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients

Current status of inherited pancreatic cancer

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