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In Reply

Institut National de la Santé et de la Recherche Médicale (INSERM), U762; and the Université Pierre et Marie Curie-Paris6, IFR65, Paris, France

The letter by Cossio et al reflects a misunderstanding of the message we wanted to deliver in our article published in the January 10, 2006, issue of the Journal of Clinical Oncology.¹ In our article, we further analyzed a panel of five mononucleotide repeat loci that we previously proposed² as sensitive and specific markers to determine the microsatellite instability (MSI) status of human tumors. We had already shown that these microsatellites were highly unstable in MSI-high (MSI-H) tumors, and monomorphic or quasimonomorphic in the general population of Eurasian origin, so that they could be used to detect microsatellite instability, at least in Eurasian patients, without referring to matching, normal DNA.

Our article¹ was an extensive analysis of the frequency of allelic variants for these five markers in a series of 1,206 individuals belonging to 55 distinct populations worldwide. We did not analyze these markers in all populations of all countries. Instead, germline DNA samples from 52 of 55 analyzed populations were obtained from the Human Genome Diversity Project-Centre d’Etude du Polymorphisme Humain diversity panel, which is the best approximation available of the world populations.³ As Cossio et al pointed out, the Brazilian population is heterogeneous with, apart from Native Americans, a very large proportion of individuals of European and African origin. In our multipopulation study, we analyzed two American Indian populations from South America, but we did not indicate that they were representative of the actual Brazilian population. We also analyzed seven population groups from sub-Saharan Africa and eight population groups from Europe. The allelic characteristics of these mononucleotide repeat loci in the actual Brazilian population can be deduced from those of the different American Indian, European, and African populations from which they originate, according to the relative frequencies of these origins. Accordingly, because Cossio et al report that 146 million of 188 million inhabitants of Brazil claim at least 10% sub-Saharan African ancestry, it is not surprising that the actual Brazilian population presents a relatively high percentage of size variants for the BAT-25 and BAT-26 markers. We showed that BAT-25 and BAT-26 variant allele frequencies can be as high as 57% and 15% in the San and Biaka pygmy populations, respectively, and within a 4.0% to 12.5% range in less isolated African populations like the Yoruba from Nigeria or Mandenka from Senegal.

As we were aware of worldwide allelic variation at these marker loci, we proposed that five mononucleotide repeats, instead of one or two, should be analyzed. We showed that 99.8% of the worldwide population that we examined did not present more than two markers of the pentaplex with variant alleles.¹ The three exceptions (with three variant alleles) belong to specific populations of the Biaka pygmy and San people. Since we confirmed that MSI-H tumors showed instability in at least four markers, and more frequently in five of the markers, we concluded that these five markers could be used, without referring to matching normal DNA, to determine the MSI status of tumors from all human populations. We can affirm that this fact is also true for Brazilian patients, whatever their ethnic background, provided that the five markers of the pentaplex are analyzed.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Buhard O, Cattaneo F, Wong YF, et al: Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors. J Clin Oncol 24:241-251, 2006[Abstract/Free Full Text]

2. Suraweera N, Duval A, Reperant M, et al: Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123:1804-1811, 2002[CrossRef][Medline]

3. Cann HM, de Toma C, Cazes L, et al: A human genome diversity cell line panel. Science 296:261-262, 2002[Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Buhard, O. Articles by Hamelin, R. Search for Related Content PubMed Articles by Buhard, O. Articles by Hamelin, R. Social Bookmarking                            What's this?