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Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil.

Moreira-Nunes CA, Barros MB, do Nascimento Borges B, Montenegro RC, Lamarão LM, Ribeiro HF, Bona AB, Assumpção PP, Rey JA, Pinto GR, Burbano RR - Hered Cancer Clin Pract (2014)

Bottom Line: No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH.The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively.The ancestors of the two families carrying these mutations had originated from those continents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.

ABSTRACT

Background: Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil.

Methods: Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern.

Results: No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents.

Conclusion: This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study.

No MeSH data available.


Related in: MedlinePlus

Pedigrees of hereditary diffuse gastric cancer families. (A), (B), (C) and (D) represents the four families presented in this study. The numbers present under the symbols represent the age at diagnosis. The solid symbols represent the affected members with confirmed diffuse gastric cancer diagnoses. Upper left arrows indicate the probands.
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Figure 1: Pedigrees of hereditary diffuse gastric cancer families. (A), (B), (C) and (D) represents the four families presented in this study. The numbers present under the symbols represent the age at diagnosis. The solid symbols represent the affected members with confirmed diffuse gastric cancer diagnoses. Upper left arrows indicate the probands.

Mentions: Of these 27 patients, nine (33.4%) had been previously diagnosed with diffuse gastric cancer, whereas the remaining patients did not have any type of gastric tumor. Among the patients diagnosed with DGC, the age at diagnosis ranged from 27–67 years.After the retrospective study and using information collected from the analyzed patients, it was possible to identify relatives with a history of DGC and other types of tumors (Figure 1).


Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil.

Moreira-Nunes CA, Barros MB, do Nascimento Borges B, Montenegro RC, Lamarão LM, Ribeiro HF, Bona AB, Assumpção PP, Rey JA, Pinto GR, Burbano RR - Hered Cancer Clin Pract (2014)

Pedigrees of hereditary diffuse gastric cancer families. (A), (B), (C) and (D) represents the four families presented in this study. The numbers present under the symbols represent the age at diagnosis. The solid symbols represent the affected members with confirmed diffuse gastric cancer diagnoses. Upper left arrows indicate the probands.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150117&req=5

Figure 1: Pedigrees of hereditary diffuse gastric cancer families. (A), (B), (C) and (D) represents the four families presented in this study. The numbers present under the symbols represent the age at diagnosis. The solid symbols represent the affected members with confirmed diffuse gastric cancer diagnoses. Upper left arrows indicate the probands.
Mentions: Of these 27 patients, nine (33.4%) had been previously diagnosed with diffuse gastric cancer, whereas the remaining patients did not have any type of gastric tumor. Among the patients diagnosed with DGC, the age at diagnosis ranged from 27–67 years.After the retrospective study and using information collected from the analyzed patients, it was possible to identify relatives with a history of DGC and other types of tumors (Figure 1).

Bottom Line: No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH.The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively.The ancestors of the two families carrying these mutations had originated from those continents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biological Science Institute, Federal University of Para, Belem, PA 66075110, Brazil.

ABSTRACT

Background: Hereditary diffuse gastric cancer (HDGC) is a hereditary autosomal inherited syndrome associated with CDH1 germline mutations. In Brazil, gastrointestinal tumors are among the most prevalent tumor types and constitute a serious public health problem, especially in the northern and northeastern regions. This study aimed to investigate germline mutations, methylation pattern and genomic rearrangements in the CDH1 gene and quantitative changes in the DNA of HDGC patients in northern and northeastern Brazil.

Methods: Twenty-seven DNA samples from the members of four families affected by HDGC were analyzed using array comparative genomic hybridization (aCGH), DNA sequencing and methylation pattern.

Results: No evidence of gain and loss events or any rearrangements were found in any of the samples tested using aCGH. No promoter region hypermethylation was observed either. Two of the four families presented different types of germline mutations. The 185G > T and 1018A > G germline mutations detected in this study have been described in Asian and European families, respectively. The ancestors of the two families carrying these mutations had originated from those continents.

Conclusion: This is the first study to evaluate CDH1 gene germline mutations in Brazilian families with HDGC. In our study, 50% of the families showed no CDH1 gene alterations, and it is possible that in regions with a high incidence of gastric cancer, such as northern and northeastern Brazil, environmental factors might have induced the different genetic alterations analyzed in this study.

No MeSH data available.


Related in: MedlinePlus