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(Drug information on 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.
