hMLH1 andhMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Rossi, Benedito Mauro; Lopes, Ademar; Ferreira, Fábio Oliveira; Nakagawa, Wilson Toshihiko; Ferreira, Claudia Cristina Napoli; Rocha, José Cláudio; Simpson, Catarina C.; Simpson, Andrew J.G.

doi:10.1007/bf02573891

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…However, mutations in Colombian families were present more frequently in MLH1 than MSH2 as compared to our cohort [32]. Furthermore, the studies from Uruguay (461 patients) [33] and Brazil (25 families) [34] showed similar results with MLH1 as the most frequently mutated gene in their studies. A study of South American LS families from Brazil (101 families), Argentina (16 families) and Uruguay (6 families), demonstrated that 56.3% of the MMR mutations were found on the MLH1 gene [28].…”

Section: Discussionsupporting

confidence: 78%

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome

et al. 2015

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Lynch Syndrome (LS) is an inherited form of colorectal cancer caused by germline mutations in the Mismatch Repair (MMR) genes. It accounts for approximately 5% of all colorectal cancers. The prevalence of Lynch Syndrome among US Hispanics is unknown. The objective of this study was to describe the germline mutations of Lynch Syndrome in Caribbean Hispanics from Puerto Rico and Dominican Republic. A total of 89 subjects were recruited through the Puerto Rico Familial Colorectal Cancer Registry and were classified according to Amsterdam and Bethesda clinical guidelines. For those tumors with lack of expression of MMR protein, gene sequencing was ordered. A total of 35 individuals with deficient MMR system were identified: 22 had MMR mutations and 13 had tumors with absent MMR protein expression. Our results show that the mutation spectrum of Caribbean Hispanic LS patients was composed mostly of MSH2 (66.7 %) mutations, followed by MLH1 (25.0 %). One mutation was identified in MSH6 (8.3 %). A previously unidentified mutation in MLH1 gene c.2044_2045del was found in one Caribbean Hispanic family. MMR mutation-positive individuals were found to be more likely to have a prominent family history of CRC and tumors located at the proximal colon. Compared to MSH2 mutation carriers, MLH1 mutation-positive individuals were more likely to have a strong family history of CRC and LS associated cancers. Furthermore, insurance coverage for genetic testing was found to be limited in the study population with 65.1% of the individuals recruited were denied coverage. This report presents the first description of the mutation spectrum and clinicopathologic characteristics of LS Caribbean Hispanics patients.

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Section: Discussionsupporting

confidence: 78%

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome

et al. 2015

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“…The mutation spectrum is predominated by MLH1 (60%) and MSH2 (40%) mutations [3,19-22], but the seemingly larger contribution than the 42% and 33% reported in the InSIGHT database could reflect failure to test for MSH6 and PMS2 mutations in most South American studies [1]. Referral bias in populations that have more recently been screened for mutations represents a potential limitation, but the strong contribution from MLH1 and MSH2 could also reflect population structure [2,4,5,7]. Frameshift mutations and nonsense mutations were the most common types of mutations, which are in agreement with findings from other populations [1,23-26], with hotspots in exons 16 and 18 of MLH1 and in exon 13 of MSH2 (Figure 2b).…”

Section: Discussionmentioning

confidence: 99%

“…Families that fulfilled the Amsterdam criteria [8,9] and/or the Bethesda guidelines [10] were selected from the hereditary cancer registries at the Hospital Italiano (Buenos Aires, Argentina), the Hospital de las Fuerzas Armadas (Montevideo, Uruguay), the Clinica Los Condes (Santiago, Chile), the Barretos Cancer Hospital (Barretos, Brazil) and from two databases in Colombia and in Southeastern Brazil (Figure 1, Table 1) [2,3,5,11]. Patients were informed about their inclusion into the registries, which generally contained data on family history, age at onset and results of genetic testing.…”

Section: Methodsmentioning

confidence: 99%

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Mutation spectrum in South American Lynch syndrome families

Dominguez‐Valentin

Nilbert

Wernhoff

et al. 2013

Hered Cancer Clin Pract

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BackgroundGenetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.MethodsWe compiled data from publications and hereditary cancer registries to characterize the Lynch syndrome mutation spectrum in South America. In total, data from 267 families that fulfilled the Amsterdam criteria and/or the Bethesda guidelines from Argentina, Brazil, Chile, Colombia and Uruguay were included.ResultsDisease-predisposing mutations were identified in 37% of the families and affected MLH1 in 60% and MSH2 in 40%. Half of the mutations have not previously been reported and potential founder effects were identified in Brazil and in Colombia.ConclusionThe South American Lynch syndrome mutation spectrum includes multiple new mutations, identifies potential founder effects and is useful for future development of genetic testing in this continent.

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“…For example, MSH2 mutation carriers appear to have a higher risk of developing extra-colonic cancer than individuals with MLH1 mutation [7, 15, 16]. In addition, the frequency and the types of mutations are reported to differ in different geographical areas, therefore, the frequency of extra-colonic cancer associated with LS may be different in different populations [17–19]. …”

Section: Introductionmentioning

confidence: 99%

Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry

et al. 2012

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The spectrum of cancers seen in a hospital based Lynch syndrome registry of mismatch repair gene mutation carriers was examined to determine the distribution of cancers and examine excess cancer risk. Overall there were 504 cancers recorded in 368 mutation carriers from 176 families. These included 236 (46.8 %) colorectal and 268 (53.2 %) extracolonic cancers. MLH1 mutation carriers had a higher frequency of colorectal cancers whereas MSH2, MSH6 and PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant. Men had fewer extracolonic cancers than colorectal (45.3 vs. 54.7 %), whereas women had more extracolonic than colorectal cancers (59.0 vs. 41.0 %). The mean age at diagnosis overall for extracolonic cancers was older than for colorectal, 49.1 versus 44.8 years (P ≤ 0.001). As expected, the index cancer was colorectal in 58.1 % of patients and among the extracolonic index cancers, endometrial was the most common (13.8 %). A significant number of non-Lynch syndrome index cancers were recorded including breast (n = 5) prostate (n = 3), thyroid (n = 3), cervix (n = 3), melanoma (n = 3), and 1 case each of thymoma, sinus cavity, and adenocarcinoma of the lung. However, standardized incidence ratios calculated to assess excess cancer risk showed that only those cancers known to be associated with Lynch syndrome were significant in our sample. We found that Lynch syndrome patients can often present with cancers that are not considered part of Lynch syndrome. This has clinical relevance both for diagnosis of Lynch syndrome and surveillance for cancers of different sites during follow-up of these patients.

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hMLH1 andhMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Cited by 14 publications

References 39 publications

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome

Mutation spectrum in South American Lynch syndrome families

Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry

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