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[Cancer Research 61, 5950-5951, August 2001]
© 2001 American Association for Cancer Research


Letters to the Editor

Correspondence re: P. P. Claudio et al., Mutations in the Retinoblastoma-related Gene RB2/p130 in Primary Nasopharyngeal Carcinoma. Cancer Res., 60: 8–12, 2000.

Steven G. Gray, Xiang Guo, Darek Kedra and Bin T. Teh

Laboratory for Clinical Genetics Van Andel Research Institute 333 Bostwick NE Grand Rapids, Michigan 49503

Xiang Guo and Hua-Qing Min

Department of Nasopharyngeal Carcinoma Cancer Center Sun Yat-sen University of Medical Sciences Guangzhou 510060 China

In a recent issue of Cancer Research, Claudio et al. (1) reported the presence of mutations within exons of the RB2/p130 gene in NPC.1 In their report concerning NPC, the authors found mutations in 3 of 10 (30%) primary tumors examined. Of interest was the fact that some of the samples contained multiple frameshift mutations within different exons (1) . The authors conclude that multiple hot spots may be present in this gene, which may be important for NPC carcinogenesis. We have undertaken an examination of 20 primary NPC tumors of Chinese origin and two NPC-derived cell lines (Hone 1-2 and HK-1) and subjected them to single strand conformational polymorphism analysis using the same primers and methodology as described by the authors (1) . Surprisingly, no mutations were observed using single strand conformational polymorphism for any of the NPCs examined. In light of this discovery, we examined the report by Claudio et al. (1) in more detail. A closer examination of the mutation chromatograms presented in Fig. 1Citation , which is published in the report, makes one doubtful of the validity of the "mutations." All of the "mutations" shown have accompanying peaks (see arrows) in one way or another, which should not be considered as "mutations" but rather as background artifacts. We have also consulted independent experts who shared our opinion. In view of the lack of support for the important findings that the authors have claimed and the fact that their results are now being quoted in high-quality papers (2) , we feel that there is an urgency to resolve this issue.



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Fig. 1.

 
Interestingly, doubts about the validation process of the mutations by the same group in a separate paper (3) have also risen from an analysis of lung tumors by Modi et al. (4) . In this report, the authors examined a large number of lung tumors for the expression of RB-related gene family proteins. Their results showed that only full-length protein was present in all primary tumors examined. Their result was in contrast to the results for lung tumors presented by Giordano’s research group in this journal (3) . According to this report, mutations involving point mutations, frameshifts, and stop codons were present in 78.5% of tumors. Using the methodology and primers from this report, Modi et al. (4) then tested for mutations in 11 lung cancer cell lines. They detected wild-type RB2 sequence from exons 19, 20, and 22 from all of the cell lines. However, using the forward primer to sequence from the exon 21 PCR products, Modi et al. (4) found multiple, heterozygous missense alterations distributed equally among the exon and intron sequences for all 11 cell lines. This could not be confirmed using the reverse primer, and cloning of the PCR product followed by sequencing using a vector sequencing primer (T7) also found no mutations. Modi et al. (4) conclude that the mutations presented for lung tumors by Claudio et al. (3) in fact represent a suboptimal analysis rather than true mutations per se.

FOOTNOTES

1 The abbreviation used is: NPC, nasopharyngeal carcinoma. Back

Received 1/ 2/01. Accepted 6/ 1/01.

REFERENCES

  1. Claudio P. P., Howard C. M., Fu Y., Cinti C., Califano L., Micheli P., Mercer E. W., Caputi M., Giordano A. Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res., 60: 8-12, 2000.[Abstract/Free Full Text]
  2. Paggi M. G., Giordano A. Who is the boss in the retinoblastoma family? The point of view of Rb2/p130, the little brother. Cancer Res., 61: 4651-4654, 2001.[Abstract/Free Full Text]
  3. Claudio P. P., Howard C. M., Pacilio C., Cinti C., Romano G., Minimo C., Maraldi N. M., Minna J. D., Gelbert L., Leoncini L., Tosi G. M., Hicheli P., Caputi M., Giordano G. G., Giordano A. Mutations in the retinoblastoma-related gene RB2/p130 in lung tumors and suppression of tumor growth in vivo by retrovirus-mediated gene transfer. Cancer Res., 60: 372-382, 2000.[Abstract/Free Full Text]
  4. Modi S., Kubo A., Oie H., Coxon A. B., Rehmatulla A., Kaye F. J. Protein expression of the RB-related gene family and SV40 large T antigen in mesothelioma and lung cancer. Oncogene, 19: 4632-4639, 2000.[Medline]



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Cancer Res., August 1, 2001; 61(15): 5952 - 5953.
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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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