Comprehensive Molecular Portraits of Human Breast Tumours
Nature, 2012 · paper · Biomedicine
Analyzes primary breast cancers from 825 patients across six molecular platforms. Reports four main breast cancer classes, only three genes (TP53, PIK3CA, GATA3) mutated in over 10% of tumours, and many molecular similarities between basal-like breast and high-grade serous ovarian tumours.
Checked: PDF from nature.com, fetched 4 Oct 2026. Page numbers are those of that PDF.
2 findings
Reference or label "the HER2E mRNA subtype typically showed high aneuploidy, the highest somatic mutation rate (Table 1)": Table 1 contains no mutation rate; the subtype mutation rates (0.84, 1.38, 2.05, 1.68 per Mb, HER2E highest) are in Figure 1.
- p. 5 HER2-based classifications, last paragraph
the highest somatic mutation rate (Table 1)
- p. 7 Table 1
Highlights of genomic, clinical and proteomic features of subtypes
- p. 2 Figure 1, far-right panel
2.05
- p. 7 Table 1
DNA mutations
Judge's note: Sentence read on the page-5 crop; Table 1 read on the page-7 image and crop. Table 1's rows give gene-level mutation percentages, copy number, methylation and protein features, and no overall mutation rate; its 'DNA mutations' row does not show HER2E as highest (TP53 84% basal-like vs 75% HER2E). The average mutation rate per subtype is printed in the far-right panel of Figure 1 (HER2E 2.05), so the pointer for the mutation rate should be Fig. 1. Table 1 does support the aneuploidy part of the sentence.
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Reference or label "RUNX1 functions as an ER 'DNA tethering factor'32": reference 32 is "Daub, H. et al. Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell 31, 438–448 (2008)", which by its title does not concern RUNX1 or oestrogen-receptor tethering.
- p. 4 Luminal/ER+ summary analysis, first paragraph
RUNX1 functions as an ER ‘DNA tethering factor’32
- p. 8 Reference 32
Daub, H. et al. Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell 31, 438–448
- p. 8 Reference 32
Daub, H. et al. Kinase-selective enrichment enables quantitative
- p. 8 Reference list, ref. 32
Daub, H. et al. Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
Only the authors can say what is right here.
Judge's note: Superscript 32 confirmed on the page-4 crop; entry 32 read on the page-8 crop. The entry is a kinome phosphoproteomics paper. Neighbouring entries 31 (RPPA technical assessment) and 33 (PARADIGM) are cited correctly for their own claims and do not fit this one either, and no entry in the list has a title about RUNX1 and ER, so the intended source appears to be missing or misnumbered. Judged from the title only; the cited paper itself is not among the files, hence a query to the authors for the intended reference.
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18 minor (typos and the like; most checked by the judge only)
Wording "identifying 30,626 somatic mutations comprised of 28,319 point mutations, 4 dinucleotide mutations, and 2,302 insertions/deletions": the three components sum to 30,625, one fewer than the stated total.
- p. 1 Significantly mutated genes in breast cancer, first sentence
identifying 30,626 somatic mutations comprised
- p. 1 same sentence
of 28,319 point mutations, 4 dinucleotide mutations, and 2,302
- p. 1 Significantly mutated genes in breast cancer, first paragraph
30,626 somatic mutations comprised of 28,319 point mutations, 4 dinucleotide mutations, and 2,302 insertions/deletions
- p. 1 Significantly mutated genes in breast cancer, first paragraph
30,626 somatic mutations comprised of 28,319 point mutations, 4 dinucleotide mutations, and 2,302
Only the authors can say what is right here.
Judge's note: Read on the page-1 crop. 28,319 + 4 + 2,302 = 30,625, not 30,626. The point-mutation subtypes in the next sentence (6,486 + 19,045 + 1,437 + 26 + 506 + 819) do sum to 28,319, so the off-by-one lies in the total, the dinucleotide count or the indel count; no further mutation class is named anywhere in the article. Real but a difference of one in about 30,000, so rated minor; only the authors can say which figure is off.
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Wording Introduction says "Triple-negative breast cancers (TNBCs ...), also known as basal-like breast cancers6", while page 6 says "~75% of TNBCs are basal-like with the other 25% comprised of all other mRNA subtypes6" and reports 76 TNBCs, 81 basal-like and 65 that were both.
- p. 1 Introduction, first paragraph
also known as basal-like breast cancers6
- p. 6 Basal-like summary analysis
75% of TNBCs are basal-like with the other 25% com- prised of all other mRNA subtypes6
- p. 6 Basal-like summary analysis
76 TNBCs, 81 basal-like, and 65 that were both TNBCs and basal-like
Judge's note: Both passages read on the crops (page 1 introduction, page 6 basal-like section); both cite reference 6. The introduction equates the two groups, while the later text and the paper's own counts (65 of 76 TNBCs basal-like; 65 of 81 basal-like TNBC) distinguish them. The introduction is loose shorthand rather than a wrong number, so this is a wording inconsistency.
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Wording The text says "A recent paper12 performed exome sequencing of 102 TNBCs"; the count of tumours in ref. 12 (Shah et al., Nature 486, 395-399, 2012) should be checked against that paper.
- p. 6 Basal-like summary analysis
exome sequencing of 102 TNBCs
- p. 8 Reference 12
The clonal and mutational evolution spectrum of primary triple-
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that Shah et al. 2012 reported 104 primary TNBC cases (and exome-sequenced only a subset of them). The page image of p6 does read "exome sequencing of 102 TNBCs" and ref. 12 on p8 is Shah et al. Nothing in the article gives the cited study's sample size, so the figure cannot be verified from the files; raised as a query only.
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Typo "The recent development of additional high information content assays ... and protein expression, provide further opportunities": singular subject 'development' with plural verb 'provide' (should be 'provides').
- p. 1 Introduction, second paragraph
expression, provide further opportunities to characterize
Judge's note: Read on the page-1 crop; the sentence is printed as quoted. Subject-verb disagreement, cosmetic.
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Typo Table 1, HER2E column, Copy number row prints the gene symbol as "ERRB2 amp (71%)"; the gene is ERBB2, as in "HER2 (also called ERBB2)" on p1 and in Figs 1 and 4.
- p. 7 Table 1, Copy number row, HER2E column
ERRB2 amp (71%)
- p. 1 Introduction
HER2 (also called ERBB2)
- p. 2 Mutations and mRNA-expression subtype associations
HER2 amplification (80%)
Judge's note: Crop and page image of p7 show italic 'ERRB2' in the Table 1 cell; the introduction (p1), Fig. 1 column header (p2) and Fig. 4a (p6) all print ERBB2. Plain misspelling. The second point raised (80% HER2 amplification in the text on p2 versus 71% in Table 1) is not confirmed: Table 1's footnote says its percentages are based on the 466-tumour overlap list and the cell specifies '17q12 focal' amplification, whereas the p2 text refers to the HER2E group of Fig. 1 (n = 57) and says only 'amplification'; different sample set and possibly different definition, so the two figures are not shown to be the same quantity.
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Typo "DNA methylation group 3 (N = 49)": capital N for a sample size, where the rest of the article uses lower-case n (e.g. "n = 547", "n = 8").
- p. 3 DNA methylation, supervised analysis
(N 5 49)
Judge's note: Read on the page-3 crop: italic capital 'N = 49'. Elsewhere the article prints lower-case italic n. Notation inconsistency only; either form is acceptable.
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Typo "interplay between PIK3CA, MAP3K and MAP2K4 signalling": 'MAP3K' printed where the gene MAP3K1 is meant.
- p. 4 Luminal/ER+ summary analysis, right column
interplay between PIK3CA, MAP3K and MAP2K4 signalling
Judge's note: Read on the page-4 crop: 'MAP3K' is set in gene-symbol italics between PIK3CA and MAP2K4. The paragraph before and after, and Figure 4a, concern MAP3K1; the final digit has been dropped.
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Typo "Almost all MAP3K1and MAP2K4 mutations": missing space between 'MAP3K1' and 'and'.
- p. 4 Luminal/ER+ summary analysis, right column
Almost all MAP3K1and
Judge's note: Read on the page-4 crop: the italic 'MAP3K1' runs directly into roman 'and' with no word space, unlike 'MAP3K1 and' on the next line. This is in the typeset page, not an extraction artefact.
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Typo The gene is written "IGFR1" in the text (page 5 "receptors (FGFRs) and IGFR1"; page 8 "FGFR1, FGFR2, IGFR1, KIT, MET") but "IGF1R" in Figure 4a.
- p. 5 Text below Figure 3 caption (end of luminal section)
receptors (FGFRs) and IGFR1, as well as cyclin D1
- p. 8 First line of page
FGFR1, FGFR2, IGFR1, KIT, MET
- p. 6 Figure 4a
IGF1R
- p. 5 Top of right-hand text, end of luminal section
receptors (FGFRs) and IGFR1
Judge's note: Both text instances read on the crops, in gene-symbol italics; Figure 4a (page 6 crop) labels the same gene IGF1R in the module diagram and the fingerprint. The paper is internally inconsistent; the figure's form is the one used for the gene in the paper's own data display, so the text spelling is the one to change.
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Typo The key of Figure 5a reads "Homzygous deletion"; it should read "Homozygous deletion", as in the Figure 4 key.
- p. 7 Figure 5a legend
Homzygous deletion
- p. 6 Figure 4 legend
Homozygous deletion
Judge's note: Crop of Fig. 5a (p7) clearly shows 'Homzygous deletion' as the last key entry; the Fig. 4 key on p6 reads 'Homozygous deletion'. Misspelling in the figure artwork.
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Typo Table 1, PIK3CA/PTEN pathway row, Luminal B column reads "PIK3CA mut (32%) PTEN mut/loss (24%) INPP4B loss (16%)" with no semicolons between the three items, unlike the other three columns of the same row.
- p. 7 Table 1, PIK3CA/PTEN pathway row, Luminal B column
PIK3CA mut (32%) PTEN mut/loss
- p. 7 Table 1, PIK3CA/PTEN pathway row, Luminal B
PIK3CA mut (32%) PTEN mut/loss (24%) INPP4B loss (16%)
Judge's note: Page image and crop of Table 1 (p7): Luminal A, Basal-like and HER2E cells separate the items with semicolons ('PIK3CA mut (49%); PTEN mut/loss (13%); INPP4B loss (9%)'), the Luminal B cell has none. Cosmetic; the meaning is recoverable.
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Typo Methods Summary, last sentence: "Additional integrated across-platform computational analyses were preformed including PARADIGM33 and MEMo41"; 'preformed' should be 'performed'.
- p. 8 Methods Summary, last sentence
lyses were preformed including PARADIGM
- p. 8 Methods Summary, last sentence
lyses were preformed including PARADIGM33 and MEMo41
- p. 8 Methods summary
analyses were preformed including PARADIGM
- p. 8 Methods summary, last sentence
were preformed including PARADIGM
Judge's note: Page image of p8 shows 'lyses were preformed including PARADIGM33 and MEMo41'. Plain misspelling.
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Typo Concluding remarks: "The integrated molecular analyses of breast carcinomas that we report here significantly extends our knowledge base"; plural subject 'analyses' with singular verb 'extends'.
- p. 8 Concluding remarks, first sentence
report here significantly extends our knowledge base
Judge's note: Read on page image p8. Subject is 'analyses' (plural), verb is 'extends'; should be 'extend'. Grammar slip only.
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Typo Author Contributions gives "protein analysis, W.L., R.G.W.V., G.B.M." while the author list prints the name as "Roel R. G. Verhaak"; the initials do not match (R.G.W.V. versus R.R.G.V.).
- p. 9 Author Contributions
protein analysis, W.L., R.G.W.V., G.B.M.
- p. 9 Author list, MD Anderson Cancer Center
Roel R. G. Verhaak
Only the authors can say what is right here.
Judge's note: Crops of p9: contributions paragraph reads 'W.L., R.G.W.V., G.B.M.'; the MD Anderson author list reads 'Wenbin Liu40, Roel R. G. Verhaak40'. No other listed author has initials R.G.W.V., so the same person is meant and one of the two forms is misprinted. Which is right is for the authors to say.
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Typo Author Contributions: "mRNA microarray analysis; K.A.H., C.F.;" and "copy number analysis; A.D.C., M.M.;" use a semicolon after the role where every other entry uses a comma.
- p. 9 Author Contributions
microarray analysis; K.A.H., C.F.;
- p. 9 Author Contributions
copy number analysis; A.D.C., M.M.;
Judge's note: Crop of p9 shows 'DNA sequence analysis, D.C.K., L.D.; mRNA microarray analysis; K.A.H., C.F.; miRNA sequence analysis, A.G.R., A.C.; ... copy number analysis; A.D.C., M.M.; protein analysis, W.L., ...'. The pattern elsewhere is 'role, initials;'. Punctuation slip in two entries.
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Typo Affiliation 63 reads "MD Anderson Cancer Center, Houston, Texas 07703, USA"; the other MD Anderson affiliations (33, 38, 39, 40, 70) give "Houston, Texas 77030".
- p. 10 Affiliation 63
MD Anderson Cancer Center, Houston, Texas 07703, USA
- p. 10 Affiliation 38
Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
- p. 10 Affiliation 70
MD Anderson Cancer Center, Houston, Texas77030,USA
- p. 10 Affiliation 63
Houston, Texas 07703, USA
Judge's note: Crop and page image of p10 show 'Houston, Texas 07703, USA' in affiliation 63, and 'Houston, Texas 77030, USA' in affiliations 33, 38-40 and 70 for the same institution (27 and 28 give 77054). The digits of 77030 are transposed. The inconsistency is internal to the page, so no outside fact is needed. The duplicated 'Chapel Hill' in affiliation 18, also mentioned here, is handled in C029.
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Typo Affiliation 18 reads "University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, North Carolina 27599, USA"; the city is given twice.
- p. 10 Affiliation 18
Carolina at Chapel Hill, Chapel Hill, Chapel
- p. 10 Affiliation 18
University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, North Carolina 27599
- p. 10 Affiliation 18
Chapel Hill, Chapel Hill, Chapel Hill, North Carolina 27599
Judge's note: Crop of p10: affiliation 18 prints 'at Chapel Hill, Chapel Hill, Chapel Hill, North Carolina 27599', whereas affiliations 14-17 and 19 print 'at Chapel Hill, Chapel Hill, North Carolina 27599'. Duplicated phrase.
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Typo Affiliation 46 reads "The Ohio State University College of Medicine, Department Pediatrics, Columbus, Ohio 43205, USA"; 'of' is missing ('Department of Pediatrics').
- p. 10 Affiliation 46
Department Pediatrics, Columbus, Ohio 43205
- p. 10 Affiliation 46
Department Pediatrics
Judge's note: Page image of p10: affiliation 45 reads 'Department of Pathology', affiliation 46 reads 'Department' at the line end followed by 'Pediatrics' on the next line with no 'of'. Missing word, not a spacing artefact.
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