Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

Abstract

Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10 157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of dierent origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidenti®ed tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.

Genetic alterations of chromosome band 9p21 – 22 in head and neck cancer are not restricted to p16INK4a

“…Allelic loss at 9p21 ± 22 in HNSCC To further re®ne the extent of genetic alterations at 9p21 ± 22 in primary HNSCC, a paired set of 21 tumors and blood specimens that were shown previously to exhibit LOH at 3p and other regions (Waber et al, 1996;Kirkpatrick et al, 1997;Li et al, 1994), were tested for LOH using eight di erent highly polymorphic markers surrounding p16 INK4a at 9p21 ± 22 ( Figure 1 and Table 1). The markers were between 62 and 90 percent informative (Figure 2).…”

“…Frozen sections were used by a pathologist to determine the margins of the tumor, and tumor samples were obtained from the center of these specimens minimizing the amount of contaminating normal tissue. The demographic and clinical features of these patients has been summarized previously (Waber et al, 1996;Kirkpatrick et al, 1997;Li et al, 1994). All of the patients smoked tobacco and ingested alcohol.…”

“…DNA digested with HindIII alone is depicted on the left as a control 9p21 ± 22 and p16 INK4a in head and neck cancer P Waber et al ing small oligonucleotide (commonly`CA') repeats interspersed frequently throughout the human genome (Weber and May, 1989). This method was described in detail for the analysis of primary HNSCC samples previously (Waber et al, 1996;Kirkpatrick et al, 1997;Li et al, 1994). Oligonucleotide primer sequences were obtained from the Genome Data Base or Research Genetics (Huntsville, AL) (MapPairs) and are listed in Table 2.…”

“…Nevertheless, although genetically altered, morphologically normal mucosa is polyclonal whereas adjacent tumor is clonal (Lee et al, 1994a). Although RB1 has been localized to a region of frequent allelic loss on chromosome 13 in HNSCC, speci®c genetic alterations of this gene are relatively uncommon (Lee et al, 1993(Lee et al, , 1994bLi et al, 1994); the same is true for BRCA2 which is also located near a site of LOH at 13q in HNSCC (Kirkpatrick et al, 1997).…”

BRCA1 and BRCA2 Mutations in Women from Shanghai China

“…The complete coding regions and exon-intron boundaries for both the BRCA1 and BRCA2 genes were screened for DNA sequence variants by single-strand conformation polymorphism assay. Amplification of coding regions used both primers reported previously (13)(14)(15) Multiplex reactions of up to three different PCR products were loaded on 0.5tϫ MDE gels. Electrophoresis was performed at room temperature for 16 -20 h at 6 W. Exons 6, 11h, and 13 were also run on 3% glycerol gels for 8 h at 8 W. Results were visualized by autoradiography.…”