© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 6, 463,
March 20, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Familial Multiple Myeloma: a Family Study and Review of the Literature
Affiliations of authors: Creighton University School of Medicine, Omaha, NE; University of Nebraska Medical Center, Omaha.
Correspondence to: Henry T. Lynch, M.D., Creighton University School of Medicine, Preventive Medicine and Public Health, 719 North 24th St., Omaha, NE 68102 (e-mail: htlynch{at}creighton.edu).
My colleagues and I are deeply appreciative of the letter from Kari Hemminki calling to our attention reference material dealing with familial risk for multiple myeloma (MM) that was not included in our manuscript (1). This work from Sweden is truly exemplary and provides us with many insights into the literature dealing with familial MM.
Sobol et al. provide an exceedingly interesting and cogent response to our paper dealing with familial MM (1), wherein we reported on three siblings with MM and two with a monoclonal gammopathy of unknown significance (MGUS). The authors appropriately stress the value of creating a "precious resource" of MM-prone families so that those individuals at inordinately high risk for MM might contribute to the molecular genetic search for predispositional germline mutations as well as for sporadic mutations. Ultimately, such molecular genetic research could provide potential targets for new therapeutic approaches to this otherwise deadly disease.
The authors found four individuals with MM through three generations. Although not specifically mentioned, we assume that there was histologic verification of the disease in each of these affected individuals. It was interesting that, in the pedigree they studied, MM was restricted to females. However, we found, while evaluating that pedigree, that there appears to be an excess of females through the three generations. Therefore, it is not surprising to find that MM in the family was restricted to females. Postmenopausal breast cancer occurred in a mother and her daughter. The proband (who did not have breast cancer but did have MM at age 58) had no deleterious mutations or polymorphisms in BRCA1. However, the proband was found to harbor a nonsense mutation, A10204T, in exon 27 of BRCA2, which corresponded to a Lys 3326 Stop substitution that is predicted to cause loss of the carboxyl-terminal 93 amino acids of the BRCA2 protein. Cautious interpretation of this finding was appropriately advised by the authors, as this specific variation has been observed in cancer patients as well as in control subjects, and thus its biologic consequence remains unclear (2,3). Sobol et al. also found that one of the MM-affected individuals had a variation in the noncoding intronic sequence of BRCA2 that corresponds to a substitution of 16 nucleotides upstream of exon 25 (IVS25–16 T/C).
We are pleased that our manuscript has provoked interest among our international colleagues. We have long believed, as do Sobol et al., that although certain forms of hereditary cancer may be rare, such families may provide important knowledge about their more commonly occurring sporadic counterparts. In turn, such hereditary cancers may provide the molecular genetic linchpin to their ultimate control.
REFERENCES
1
Lynch HT, Sanger WG, Pirruccello S, Quinn-Laquer B, Weisenburger DD. Familial multiple myeloma: a family study and review of the literature. J Natl Cancer Inst 2001;93:1479–83.
2 Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, et al. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nat Genet 1996;13:241–4.[CrossRef][Web of Science][Medline]
3 Mazoyer S, Dunning AM, Serova O, Dearden J, Puget N, Healey CS, et al. A polymorphic stop codon in BRCA2. Nat Genet 1996;14:253–4.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||