Volume 10 Supplement 1
Erratum to: Somatic mutations in cancer development
© Luzzatto; licensee BioMed Central Ltd. 2011
Published: 28 July 2011
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact us so we can address the problem.
Since publication of Environmental Health 2011, 10(Suppl 1):S12  it has been noticed that titles and captions for the figures and tables were incorrectly applied. In this full-length correction article, figures and tables have been renumbered with legends and captions applied appropriately. Some minor typographical errors have also been corrected. The inconvenience caused to readers by premature publication of the original paper is regretted.
The transformation of a normal cell into a cancer cell takes place through a sequence of a small number of discrete genetic events, somatic mutations: thus, cancer can be regarded properly as a genetic disease of somatic cells. The analogy between evolution of organisms and evolution of cell populations is compelling: in both cases what drives change is mutation, but it is Darwinian selection that enables clones that have a growth advantage to expand, thus providing a larger target size for the next mutation to hit. The search for molecular lesions in tumors has taken on a new dimension thanks to two powerful technologies: the micro-arrays for quantitative analysis of global gene expresssion (the transcriptome); and ‘deep’ sequencing for the global analysis of the entire genome (or at least the exome). The former offers the most complete phenotypic characterization of a tumor we could ever hope for – we could call this the ultimate phenotype; the latter can identify all the somatic mutations in an individual tumor – we could call this the somatic genotype. However, there is definitely the risk that while we are ‘drowned by data, we remain thirsty for knowledge’. If we want to heed the teachings of Lorenzo Tomatis, I think the message is clear: we ought to take advantage of the new powerful technologies – not by becoming their slaves, but remaining their masters. Identifying somatic mutations in a tumor is important because through a deeper understanding of the nature of that particular tumor it can help us to optimize therapy or to design new therapeutic approaches.
Two types of cancer genes
May be high
Detectable by linkage analysis
Detectable by LD analysis
Overall contribution to cancer prevalence
Could be high
Several low penetrance cancer genes are those involved in DNA repair. From Vineis et al. 
Type of tumor(s)
Head & Neck
Cervix; esophageal, head & neck; skin; stomach
With respect to the environment, I think the most lasting monumental memorial to Lorenzo is the series of IARC publications on carcinogenic agents which, in the jargon of the cognoscentes, are known simply as The Monographs. Rarely has an international agency been able to generate publications (each one the product of a collegial effort) with so much scientific content; even more rarely has this taken place consistently in dozens of volumes over some thirty years, to the extent that the Monographs are universally regarded as the ultimate authority on their individual topics; and probably never has a single person – namely Tomatis himself – through his scientific rigor, his incredible dedication, and his unique ability to catalyze consensus whenever possible, contributed so much to a successful venture of this nature.
The principles and theory of population genetics can be applied to populations of cells.
In populations of organisms
In populations of somatic cells
Creates a mutant individual/family
Creates a mutant cell/clone
No clonal growth
No visible change
No visible change
Mutation with absolute advantage
Mutant people will gradually take over
Clone will grow faster than other cells
Mutation with conditional advantage
Mutant people will increase in a certain environment
Clone will grow faster under certain conditions
In order to understand the pathogenesis of tumors we must consider their very extensive variety: not only can they arise in virtually every possible cell type in the body, but even within the set of tumors arising from a specific type of cell there is marked heterogeneity, some of it well explored and some yet to be unravelled. The somatic mutation-Darwinian selection model of cancer is appropriately versatile: we can presume, and we know in specific cases that different genes are involved: some 400 have been already identified . To this end, the methodology that has given the highest returns has been cytogenetic analysis, which has spotted (i) chromosomal translocations harbouring fusion genes or rearrangements that dysregulate gene expression, as well as (ii) loss of heterozigosity betraying deletions. In other cases somatic mutations have been discovered in genes already known to have germ-line mutations in cancer-prone families, or by deliberately testing for somatic mutations in candidate genes. Not surprisingly, many of the genes involved belong to sets that are relevant to broad functions within the cell (the buzz-term today is gene ontology): particularly the cell cycle, signalling, regulation of transcription, apoptosis and, once again, genome stability (DNA repair) [20, 21].
Some specific types of somatic mutations found in tumors. From Sjoblom et al., .
Substitutions at CG base pairs
CG to TA
CG to GC
CG to AT
Substitutions at TA base pairs
TA to CG
TA to GC
TA to AT
Substitutions at specific dinucleotides
The progress of contemporary biology has led us within thirty years from a multitude of theories about oncogenesis to the established fact that cancer is a genetic disorder of somatic cells. On the other hand, much recent literature gives the impression that there is a surplus of information, from gene expression profiles to proteomics to metabolomics, with the risk that while we are truly ‘drowned by data, we remain thirsty for knowledge’. If we want to heed the teachings of Lorenzo Tomatis, I think the message is clear: we ought to take advantage of the new powerful technologies – not by becoming their slaves, but remaining their masters. Identifying somatic mutations in a tumor is important not because it qualifies for ‘oncogenomics’, but because through a deeper understanding of the nature of that particular tumor it can help us to optimize therapy or to design new therapeutic approaches.
This article has been published as part of Environmental Health Volume 10 Supplement 1, 2011: Proceedings of the First Lorenzo Tomatis Conference on Environment and Cancer. The full contents of the supplement are available online at http://www.ehjournal.net/supplements/10/S1.
- Luzzatto L: Somatic mutations in cancer development. Environmental Health. 2011, 10 (Suppl 1): S12-10.1186/1476-069X-10-S1-S12.View ArticleGoogle Scholar
- Lijinsky W, Lee KY, Tomatis L, Buutler WH: Nitrosoazetidine--a potent carcinogen of low toxicity. Die Naturwissenschaften. 1967, 54 (19): 518-View ArticleGoogle Scholar
- Tomatis L: Identification of carcinogenic agents and primary prevention of cancer. Ann N Y Acad Sci. 2006, 1076: 1-14. 10.1196/annals.1371.039.View ArticleGoogle Scholar
- Vogelstein BaK KW: The Genetic Basis of Human Cancer. 2002, New York: McGraw-Hill, 2Google Scholar
- Offit K: Clinical cancer genetics: risk counseling and management. 1998, New York: Wiley-Liss, 1:Google Scholar
- Gramatovici M, Bennett JM, Hiscock JG, Grewal KS: Three cases of familial hairy cell leukemia. Am J Hematol. 1993, 42 (4): 337-339. 10.1002/ajh.2830420402.View ArticleGoogle Scholar
- Fraumeni JF: Epidemiologic approaches to cancer etiology. Annu Rev Public Health. 1982, 3: 85-100. 10.1146/annurev.pu.03.050182.000505.View ArticleGoogle Scholar
- Narod SA, Stiller C, Lenoir GM: An estimate of the heritable fraction of childhood cancer. Br J Cancer. 1991, 63: 993-999. 10.1038/bjc.1991.216.View ArticleGoogle Scholar
- Cannon-Albright LA, Thomas A, Goldgar DE, Gholami K, Rowe K, Jacobsen M, McWhorter WP, Skolnick MH: Familiality of cancer in Utah. Cancer Res. 1994, 54 (9): 2378-2385.Google Scholar
- Kadan-Lottick NS, Kawashima T, Tomlinson G, Friedman DL, Yasui Y, Mertens AC, Robison LL, Strong LC: The risk of cancer in twins: a report from the childhood cancer survivor study. Pediatr Blood Cancer. 2006, 46 (4): 476-481. 10.1002/pbc.20465.View ArticleGoogle Scholar
- Stephens JC, Briscoe D, O'Brien SJ: Mapping by admixture linkage disequilibrium in human populations: limits and guidelines. Am J Hum Gene. 1994, 55 (4): 809-824.Google Scholar
- Weber BL, Nathanson KL: Low penetrance genes associated with increased risk for breast cancer. Eur J Cancer. 2000, 36 (10): 1193-10.1016/S0959-8049(00)00082-4.View ArticleGoogle Scholar
- Nathanson KL, Wooster R, Weber BL: Breast cancer genetics: what we know and what we need. Nat Med. 2001, 7 (5): 552-556. 10.1038/87876.View ArticleGoogle Scholar
- Hartman M, Loy EY, Ku CS, Chia KS: Molecular epidemiology and its current clinical use in cancer management. Lancet Oncol. 2010, 11 (4): 383-390. 10.1016/S1470-2045(10)70005-X.View ArticleGoogle Scholar
- Cairns J: Mutation selection and the natural history of cancer. Nature. 1975, 255 (5505): 197-200. 10.1038/255197a0.View ArticleGoogle Scholar
- Luzzatto L, Pandolfi PP: Laukaemia: a genetic disorder of haemopoietic cells. BMJ. 1993, 307: 579-580. 10.1136/bmj.307.6904.579.View ArticleGoogle Scholar
- Cahill DP, Kinzler KW, Vogelstein B, Lengauer C: Genetic instability and darwinian selection in tumours. Trends Cell Biol. 1999, 9 (12): M57-60. 10.1016/S0962-8924(99)01661-X.View ArticleGoogle Scholar
- Greaves M: Darwinian medicine: a case for cancer. Nature Reviews. 2007, 7 (3): 213-221.Google Scholar
- Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR: A census of human cancer genes. Nature Reviews. 2004, 4 (3): 177-183. 10.1038/nrc1299.Google Scholar
- Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100 (1): 57-70. 10.1016/S0092-8674(00)81683-9.View ArticleGoogle Scholar
- Vogelstein B, Kinzler KW: Cancer genes and the pathways they control. Nat Medicine. 2004, 10 (8): 789-799. 10.1038/nm1087.View ArticleGoogle Scholar
- van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415 (6871): 530-536. 10.1038/415530a.View ArticleGoogle Scholar
- Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, Muir B, Mohapatra G, Salunga R, Tuggle JT: A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer cell. 2004, 5 (6): 607-616. 10.1016/j.ccr.2004.05.015.View ArticleGoogle Scholar
- Nelson PS: Predicting prostate cancer behavior using transcript profiles. J Urol. 2004, 172 (5 Pt 2): S28-32. discussion S33View ArticleGoogle Scholar
- Sotiriou C, Pusztai L: Gene-expression signatures in breast cancer. NEJM. 2009, 360 (8): 790-800. 10.1056/NEJMra0801289.View ArticleGoogle Scholar
- Cavalieri D, Dolara P, Mini E, Luceri C, Castagnini C, Toti S, Maciag K, De Filippo C, Nobili S, Morganti M: Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer. Oncol Res. 2007, 16 (11): 535-548. 10.3727/096504007783438376.View ArticleGoogle Scholar
- Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N: The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science. 2006, 314 (5797): 268-274. 10.1126/science.1133427.View ArticleGoogle Scholar
- Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD: Recurring mutations found by sequencing an acute myeloid leukemia genome. NEJM. 2009, 361 (11): 1058-1066. 10.1056/NEJMoa0903840.View ArticleGoogle Scholar
- Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA: Characterizing the cancer genome in lung adenocarcinoma. Nature. 2007, 450 (7171): 893-898. 10.1038/nature06358.View ArticleGoogle Scholar
- Stratton MR, Campbell PJ, Futreal PA: The cancer genome. Nature. 2009, 458 (7239): 719-724. 10.1038/nature07943.View ArticleGoogle Scholar
- Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008, 456 (7218): 66-72. 10.1038/nature07485.View ArticleGoogle Scholar
- Esteller M: Epigenetics provides a new generation of oncogenes and tumour-suppressor genes. BrJ Cancer. 2006, 94 (2): 179-183. 10.1038/sj.bjc.6602918.View ArticleGoogle Scholar
- Fraga MF, Esteller M: Towards the human cancer epigenome: a first draft of histone modifications. Cell cycle (Georgetown, Tex. 2005, 4 (10): 1377-1381. 10.4161/cc.4.10.2113.View ArticleGoogle Scholar
- McKenna ES, Roberts CW: Epigenetics and cancer without genomic instability. Cell cycle (Georgetown, Tex. 2009, 8 (1): 23-26. 10.4161/cc.8.1.7290.View ArticleGoogle Scholar
- Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L: Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci U S A. 1999, 96 (9): 5209-5214. 10.1073/pnas.96.9.5209.View ArticleGoogle Scholar
- Araten DJ, Golde DW, Zhang RH, Thaler HT, Gargiulo L, Notaro R, Luzzatto L: A Quantitative Measurement of the Human Somatic Mutation Rate. Cancer Res. 2005, 65 (18): 8111-8117. 10.1158/0008-5472.CAN-04-1198.View ArticleGoogle Scholar
- Peruzzi B, Araten DJ, Notaro R, Luzzatto L: The use of PIG-A as a sentinel gene for the study of the somatic mutation rate and of mutagenic agents in vivo. Mutat Res. 2010, 705 (1): 3-10. 10.1016/j.mrrev.2009.12.004.View ArticleGoogle Scholar
- Vineis P, Manuguerra M, Kavvoura FK, Guarrera S, Allione A, Rosa F, Di Gregorio A, Polidoro S, Saletta F, Ioannidis JP, Matullo G: A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility. J Natl Cancer Inst. 2009, 101 (1): 24-36.View ArticleGoogle Scholar
- Kaklamani VG, Hou N, Bian Y, Reich J, Offit K, Michel LS, Rubinstein WS, Rademaker A, Pasche B: TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies. J Clin Oncol. 2003, 21 (17): 3236-43. 10.1200/JCO.2003.11.524.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.