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Mutation Linked to Poor Prognosis in Head & Neck Cancer

Mutation Linked to Poor Prognosis in Head & Neck Cancer

SAN FRANCISCO—A single nucleotide polymorphism at codon 388 in the
transmembrane domain of FGFR4 is linked to poor survival in patients with head
and neck squamous cell carcinoma. The mutation (Arg388) involves the
substitution of an arginine molecule for glycine at this position on the gene.
It occurs in 45% to 50% of all humans.

Since the mutation occurs in the germ line, it is not connected to disease
initiation, said Axel Ullrich, PhD, director of the Molecular Biology
Department at the Max Planck Institute for Biochemistry, Martinsried, Germany.
But, he said, "when the patient gets cancer, it is directly connected, and
statistically highly significant, with an aggressive disease progression."

Dr. Ullrich reported the results at a news briefing at the 93rd Annual
Meeting of the American Association for Cancer Research. Dr. Sylvia Streit,
also of the Max Planck Institute, presented the paper at a minisymposium at the
meeting (abstract 4116).

Possible Protective Effect

The German researchers studied samples from 104 tumors of patients with
squamous cell head and neck cancer, using archival tissue. The tissue samples
were analyzed for the FGFR4 genotype using a method based on restriction
fragment length polymorphism.

The arginine mutation was found in 59 of the tumors, 46 heterozygous (in one
chromosome), 13 homozygous (in both chromosomes). Patients with the FGFR4
Arg388 polymorphism experienced a significantly worse overall survival,
compared with those with FGFR4 Gly388 (P = .02).

There were not enough subjects to determine if patients who were homozygous
for FGFR4 Arg388 did worse than those who were heterozygous. "We are
trying to determine that right now with another study," Dr. Ullrich said,
adding that "there’s a good possibility" that this would turn out
to be the case.

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