Cancer Genome Landscapes
2013 · paper · Biomedicine
Reviews comprehensive sequencing of common human cancers. About 140 driver genes have been found, with typically two to eight driver mutations per tumor, and these genes fall into 12 signaling pathways regulating cell fate, cell survival and genome maintenance.
1 finding
Substance Text names "the proteins DNMT1 and TET1, which covalently modify DNA" as newly discovered Mut-driver genes (53–57). The cited refs 53 (Delhommeau, NEJM 2009; 360:2289) and 56 (Ley, NEJM 2010; 363:2424) are the TET2 and DNMT3A mutation reports.
- p. 9 How Many Mut-Driver Genes Exist?, last paragraph
as well as the proteins DNMT1 and TET1, which covalently modify DNA
- p. 22 Reference list, refs 53 and 56
53. Delhommeau F, et al. N Engl J Med. 2009; 360:2289.
- p. 9 How Many Mut-Driver Genes Exist?, paragraph on chromatin
DNMT1 and TET1, which covalently modify DNA
- p. 22 References 53 and 56
Delhommeau F, et al. N Engl J Med. 2009; 360:2289.
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that refs 53 and 56 report TET2 and DNMT3A mutations, and that DNMT1/TET1 are not established recurrently mutated drivers. The p9 image shows 'DNMT1 and TET1'; DNMT1 and TET1 appear nowhere else in the text. The reference entries match on the page image.
Second check: another model agreed
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8 minor (typos and the like; most checked by the judge only)
Wording The abstract ("~140 genes that, when altered by intragenic mutations") and Box 2 item 3 attribute all ~140 Mut-driver genes to intragenic mutations. Page 10 counts 125 genes affected by subtle mutations plus 13 that are "not point-mutated" (10 amplified, 3 homozygously deleted), for 138 in total.
- p. 1 Abstract
~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis
- p. 20 Box 2, item 3
there are ~140 genes whose intragenic mutations contribute to cancer (so-called Mut-driver genes)
- p. 10 Text on table S2B
This adds 13 Mut-driver genes—10 oncogenes that are amplified and 3 tumor suppressor genes that are homozygously deleted—to the 125 driver genes
Only the authors can say what is right here.
Judge's note: Checked p1 abstract, p20 Box 2 and p10 text. Page 10 explicitly says the 13 added genes are not point-mutated but amplified or homozygously deleted, so 'intragenic mutations' does not cover all ~140. This is a wording imprecision; the count of ~140 itself is consistent with 138.
Second check: another model agreed
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Wording Text says that in medulloblastomas "the number of driver gene mutations is low (zero to two)... (Fig. 5)", but the Fig. 5 medulloblastoma panel shows blue bars of about 5% each at 3 and 4 driver mutations.
- p. 10 Dark Matter, first paragraph
the number of driver gene mutations is low (zero to two), as expected from the discussion above (Fig. 5)
- p. 29 Fig. 5, Medulloblastoma panel
Number of driver gene mutations per tumor
Judge's note: Viewed the p29 Fig. 5. Medulloblastoma oncogene+TSG bars are approximately 52%, 19%, 0%, 19%, 5%, 5% (0 to 4 mutations); about 10% of tumors fall outside 'zero to two'. The phrase could describe the typical range, so this is minor.
Second check: another model agreed
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Wording "Few individual tumors contain more than one oncogene mutation (Fig. 5)". In the Fig. 5 breast cancer panel, the red oncogene-only bars at 2, 3 and 4 are about 23%, 11% and 6%.
- p. 17 Challenges, second paragraph
Few individual tumors contain more than one oncogene mutation (Fig. 5).
- p. 29 Fig. 5, Breast Cancer panel (red bars)
Oncogene mutations
Only the authors can say what is right here.
Judge's note: Viewed the p29 Fig. 5. Breast red bars are approximately 29/29/23/11/6% for 0 to 4 oncogene mutations, so about 40% of breast tumors have more than one. The statement holds for the other panels. It is an overgeneralisation relative to the cited figure.
Second check: another model agreed
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Typo Box 1 glossary definition of Angiogenesis begins in lowercase: "the process of forming vascular conduits, including veins, arteries, and lymphatics."
- p. 1 Box 1 Glossary, Angiogenesis
the process of forming vascular conduits, including veins,
Judge's note: Page 1 crop: the neighbouring definitions (ALT, Amplification) start with a capital; this one starts with lowercase 'the'. Cosmetic.
Second check: none (judge only)
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Typo Gene symbol misspelled: "epigenetic silencing of CDK2NA and MLH1" should be CDKN2A.
- p. 11 Dark Matter, last paragraph
epigenetic silencing of CDK2NA and MLH1
- p. 15 Cell survival paragraph
such as CDKN2A,
Judge's note: The p11 image shows 'CDK2NA' in italics. The paper spells it CDKN2A on p15 and p17.
Second check: none (judge only)
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Typo Misspelling: "provides the seeds for intermetastastic heterogeneity" should read 'intermetastatic'.
- p. 12 Genetic Heterogeneity, item 1, second paragraph
provides the seeds for intermetastastic heterogeneity
- p. 12 Intratumoral heterogeneity item 1
intermetastastic heterogeneity
- p. 12 item 1 Intratumoral, end
seeds for intermetastastic heterogeneity
Judge's note: The p12 image shows 'intermetastastic'. The next item heading reads 'Intermetastatic'.
Second check: none (judge only)
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Typo Missing full stop: "genes (85) However, there is a critical difference".
- p. 12 First line of page
genes (85) However, there is a critical difference
Judge's note: The p12 top line on the image shows no period between '(85)' and 'However'.
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Typo Reference 85 "Beggs AD, et al. J Pathol. 201210.1002/path.4132" runs the year into the DOI and lacks volume/pages.
- p. 22 References, entry 85
85. Beggs AD, et al. J Pathol. 201210.1002/path.4132
Judge's note: The p22 image shows the fused '201210.1002' with no volume, page or PubMed ID, unlike neighbouring entries. Likely an ahead-of-print citation; formatting defect only.
Second check: none (judge only)