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Absence of the palladin P239S mutation in European pancreatic cancer families

Posted by plosmedicine on 31 Mar 2009 at 00:05 GMT

Author: EUROPAC and FaPaCa
Position: European registries of familial pancreatic cancer
Institution: The University of Liverpool, Städtische Kliniken Bielefeld-Mitte and The Philipps-University Marburg
Additional Authors: Emily P. Slater, Vera Amrillaeva, Volker Fendrich, Detlef K. Bartsch On behalf of FaPaCa; and Julie Earl, Louis J. Vitone, John P. Neoptolemos, William Greenhalf On behalf of Europac
Submitted Date: February 01, 2007
Published Date: February 2, 2007
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

We read with interest the article published in PLoS by Pogue-Geile et al[1] reporting an apparent mutation in the KIAA0992 splice variant of the palladin gene in a family previously reported to have a high incidence of pancreatic cancer. The same group had previously established that the 4q32-34 locus segregated with pancreatic cancer in this family by screening for pre-neoplastic lesions, which could then be used as a marker for mutation carriers[2]. In the PLoS paper the group shows that the mutation in palladin is on the 4q32-34 haplotype that segregates with the disease. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) and the German National Case Collection for Familial Pancreatic Cancer (FaPaCa) have recently shown that a mutation on 4q32-34 is unlikely to explain pancreatic cancer in a majority of our European families, but we did not rule out segregation with the disease in a minority of families[3].

Naturally we were keen to establish if the mutation seen in Family X from America was seen in any of our families and so we have sequenced the locus in 74 individuals who were either affected by pancreatic cancer or who are obligate carriers (assuming autosomal dominant inheritance) of the disease mutation (in 74 families). We have also sequenced the locus in 14 affected individuals from 14 families with Familial Multiple Mole Melanoma with cases of pancreatic cancer (FAMMM-PC)[4] and nine sporadic pancreatic cancer patients of less than 50 years of age. We did not identify the mutation in any of the individuals, neither as a heterozygote or a homozygote.

This does not of course mean that other mutations in coding or non coding regions of this variant of palladin or other variants are absent from European families. However, it is noteworthy that the phenotype of Family X is significantly different from the phenotype common to the families on the EUROPAC/FaPaCa registries. In particular the incidence of diabetes in our families is relatively low, except where the diabetes is a direct consequence of development of cancer[3], which contrasts strongly with the family harbouring the palladin mutation[1,2], where diabetes was common. It is possible that Family X (and the association with palladin mutation) is not typical of the familial pancreatic cancer syndrome.


1. Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, et al. (2006) Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med 3: e516.
2. Eberle MA, Pfutzer R, Pogue-Geile KL, Bronner MP, Crispin D, et al. (2002) A new susceptibility locus for autosomal dominant pancreatic cancer maps to chromosome 4q32-34. Am J Hum Genet 70: 1044-1048.
3. Earl J, Yan L, Vitone LJ, Risk J, Kemp SJ, et al. (2006) Evaluation of the 4q32-34 locus in European familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 15: 1948-1955.
4. Lynch HT, Brand RE, Hogg D, Deters CA, Fusaro RM, et al. (2002) Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer 94: 84-96.

No competing interests declared.