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 20 February 2018

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News

Gastric cancer in carriers of germ-line E-cadherin mutations

Young asymptomatic carriers of germ-line truncating CDH1 mutations, who belong to families with highly penetrant, hereditary diffuse gastric cancer, should have genetic counseling and consider prophylactic gastrectomy, claims an international team.

News image

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The researchers investigated the incidence of gastric cancer in young individuals with germ-line truncating mutations in the E-cadherin (CDH1) gene.

They reported their findings in the latest issue of the New England Journal of Medicine

All subjects were asymptomatic and were from two unrelated families, in which there was a history of hereditary diffuse gastric cancer.

Truncating mutations in CDH1 found in families with hereditary diffuse gastric cancer
New England Journal of Medicine

Mutation-specific predictive genetic testing was performed in all individuals. This was done by polymerase-chain reaction amplification, followed by restriction-enzyme digestion and DNA sequencing in Family 1, and by heteroduplex analysis in Family 2.

A total gastrectomy was performed, prophylactically, in 5 carriers of mutations. All of these carriers were between 22 and 40 years old. In each case, the entire mucosa of the stomach was extensively sampled for microscopic analysis.

The team identified superficial infiltrates of malignant signet-ring cells in the surgical samples from all 5 people who underwent gastrectomy.

These early diffuse gastric cancers were multifocal in 3 of the 5 cases. In one person, infiltrates of malignant signet-ring cells were present in 65 of the 140 tissue blocks analyzed, representing in aggregate less than 2% of the gastric mucosa.

Dr David G. Huntsman, of the British Columbia Cancer Agency, Vancouver, Canada, concluded on behalf of the group, "We recommend genetic counseling and consideration of prophylactic gastrectomy in young asymptomatic carriers of germ-line truncating CDH1 mutations, who belong to families with highly penetrant, hereditary diffuse gastric cancer."

N Engl J Med 2001; 344 (25): 1904-9
25 June 2001

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