In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer

Nature Genetics

Volumn 47, Issue 10, 2015, Pages 1212-1219

  Janiszewska, Michalina ^a,b,c   Liu, Lin ^a,d   Almendro, Vanessa ^a,b,c   Kuang, Yanan ^a   Paweletz, Cloud ^a   Sakr, Rita A ^e   Weigelt, Britta ^e   Hanker, Ariella B ^f   Chandarlapaty, Sarat ^e   King, Tari A ^e   Reis Filho, Jorge S ^e   Arteaga, Carlos L ^f   Park, So Yeon ^g   Michor, Franziska ^a,d   Polyak, Kornelia ^a,b,c,h,i  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^e MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^f VANDERBILT INGRAM CANCER CENTER   (United States)

^g Seoul National University   (South Korea)

^h BROAD INSTITUTE OF MIT AND HARVARD   (United States)

ⁱ HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRASTUZUMAB; ANTINEOPLASTIC AGENT; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3CA PROTEIN, HUMAN;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER RESISTANCE; CELL MUTANT; COPY NUMBER VARIATION; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE AMPLIFICATION; GENE MUTATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; GENOMICS; HER2 POSITIVE BREAST CANCER; HUMAN; HUMAN CELL; HUMAN TISSUE; MOUSE; NONHUMAN; ONCOGENE; ONCOGENE NEU; PIK3CA GENE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SINGLE CELL ANALYSIS; TREATMENT OUTCOME; BREAST NEOPLASMS; GENETICS; MUTATION; PROTO ONCOGENE;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; FEMALE; GENES, ERBB-2; GENETIC HETEROGENEITY; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; SINGLE-CELL ANALYSIS;

EID: 84942987073     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3391     Document Type: Article

References (55)

1. Marusyk A., Almendro V., & Polyak K. Intra-tumour heterogeneity: a looking glass for cancer?. Nat. Rev. Cancer 12, 323-334 (2012
2. Yap T.A., Gerlinger M., Futreal P.A., Pusztai L., & Swanton C. Intratumor heterogeneity: seeing the wood for the trees. Sci. Transl. Med. 4, 127ps10 (2012
3. Navin N., et al. Tumour evolution inferred by single-cell sequencing. Nature 472, 90-94 (2011
4. Navin N.E. Cancer genomics: one cell at a time. Genome Biol. 15, 452-464 (2014
5. Bagasra O. Protocols for the in situ PCR-amplification and detection of mRNA and DNA sequences. Nat. Protoc. 2, 2782-2795 (2007
6. Ikeda S., Takabe K., Inagaki M., Funakoshi N., & Suzuki K. Detection of gene point mutation in paraffin sections using in situ loop-mediated isothermal amplification. Pathol. Int. 57, 594-599 (2007
7. Ebina M., Martínez M., Birrer M.J., & Linnoila R.I. In situ detection of unexpected patterns of mutant p53 gene expression in non-small cell lung cancers. Oncogene 20, 2579-2586 (2001
8. Almendro V., et al. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 6, 514-527 (2014
9. Almendro V., et al. Genetic and phenotypic diversity in breast tumor metastases. Cancer Res. 74, 1338-1348 (2014
10. Park S.Y., Gönen M., Kim H.J., Michor F., & Polyak K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J. Clin. Invest. 120, 636-644 (2010
11. Bachman K.E., et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol. Ther. 3, 772-775 (2004
12. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 (2012
13. Berns K., et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12, 395-402 (2007
14. Nagata Y., et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6, 117-127 (2004
15. Wang Y., Liu Y., Du Y., Yin W., & Lu J. The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis. Curr. Med. Res. Opin. 29, 633-642 (2013
16. Rexer B.N., Chanthaphaychith S., Dahlman K.B., & Arteaga C.L. Direct inhibition of PI3K in combination with dual HER2 inhibitors is required for optimal antitumor activity in HER2+ breast cancer cells. Breast Cancer Res. 16, R9 (2014
17. Rexer B.N., & Arteaga C.L. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit. Rev. Oncog. 17, 1-16 (2012
18. Cizkova M., et al. PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups. Breast Cancer Res. 14, R28 (2012
19. Cizkova M., et al. Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab. Br. J. Cancer 108, 1807-1809 (2013
20. Deng G., et al. Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC Cancer 14, 456-467 (2014
21. Dupont Jensen J., et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin. Cancer Res. 17, 667-677 (2011
22. Jurinke C., Van den Boom D., Cantor C.R., & Koster H. Automated genotyping using the DNA MassArray technology. Methods Mol. Biol. 170, 103-116 (2001
23. Sakr R.A., et al. PI3K pathway activation in high-grade ductal carcinoma in situ-implications for progression to invasive breast carcinoma. Clin. Cancer Res. 20, 2326-2337 (2014
24. Chandarlapaty S., et al. Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer. Clin. Cancer Res. 18, 6784-6791 (2012
25. Wolff A.C., et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J. Clin. Oncol. 31, 3997-4013 (2013
26. Vogelstein B., & Kinzler K.W. Digital PCR. Proc. Natl. Acad. Sci. USA 96, 9236-9241 (1999
27. Hindson B.J., et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal. Chem. 83, 8604-8610 (2011
28. Brunelli M., et al. Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/CAP criteria. Am. J. Clin. Pathol. 131, 678-682 (2009
29. Glöckner S., Buurman H., Kleeberger W., Lehmann U., & Kreipe H. Marked intratumoral heterogeneity of c-myc and cyclinD1 but not of c-erbB2 amplification in breast cancer. Lab. Invest. 82, 1419-1426 (2002
30. Hanna W., Nofech-Mozes S., & Kahn H.J. Intratumoral heterogeneity of HER2/neu in breast cancer - A rare event. Breast J. 13, 122-129 (2007
31. Vance G.H., et al. Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines. Arch. Pathol. Lab. Med. 133, 611-612 (2009
32. Cottu P.H., et al. Intratumoral heterogeneity of HER2/neu expression and its consequences for the management of advanced breast cancer. Ann. Oncol. 19, 595-597 (2008
33. Lewis J.T., et al. Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining. Am. J. Clin. Pathol. 124, 273-281 (2005
34. Striebel J.M., Bhargava R., Horbinski C., Surti U., & Dabbs D.J. The equivocally amplified HER2 FISH result on breast core biopsy: indications for further sampling do affect patient management. Am. J. Clin. Pathol. 129, 383-390 (2008
35. Shin S.J., Hyjek E., Early E., & Knowles D.M. Intratumoral heterogeneity of HER-2/neu in invasive mammary carcinomas using fluorescence in-situ hybridization and tissue microarray. Int. J. Surg. Pathol. 14, 279-284 (2006
36. Seol H., et al. Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod. Pathol. 25, 938-948 (2012
37. Bartlett A.I., et al. Heterogeneous HER2 gene amplification: impact on patient outcome and a clinically relevant definition. Am. J. Clin. Pathol. 136, 266-274 (2011
38. Andersson J., Linderholm B., Bergh J., & Elmberger G. HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl. Immunohistochem. Mol. Morphol. 12, 14-20 (2004
39. Ng C.K., et al. Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification. Genome Biol. 16, 107-127 (2015
40. Magurran A.E. Measuring Biological Diversity (Blackwell, 2004
41. Martins F.C., et al. Evolutionary pathways in BRCA1-associated breast tumors. Cancer Discov. 2, 503-511 (2012
42. Hanker A.B., et al. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc. Natl. Acad. Sci. USA 110, 14372-14377 (2013
43. Hartigan J.A., & Wong M. A K-means clustering algorithm. Appl. Stat. 28, 100-108 (1979
44. Samuels Y., et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-573 (2005
45. Thomas R.K., et al. High-throughput oncogene mutation profiling in human cancer. Nat. Genet. 39, 347-351 (2007
46. Grundberg I., et al. In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics. Oncotarget 4, 2407-2418 (2013
47. Chang Y.F., Imam J.S., & Wilkinson M.F. The nonsense-mediated decay RNA surveillance pathway. Annu. Rev. Biochem. 76, 51-74 (2007
48. Lee J.H., et al. Highly multiplexed subcellular RNA sequencing in situ. Science 343, 1360-1363 (2014
49. Giesen C., et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Methods 11, 417-422 (2014
50. Hammond M.E., et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch. Pathol. Lab. Med. 134, 907-922 (2010
51. Wolff A.C., et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch. Pathol. Lab. Med. 138, 241-256 (2014
52. Marusyk A., et al. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature 514, 54-58 (2014
53. Frey U.H., Bachmann H.S., Peters J., & Siffert W. PCR-amplification of GC-rich regions: slowdown PCR. Nat. Protoc. 3, 1312-1317 (2008
54. Duprez R., et al. Immunophenotypic and genomic characterization of papillary carcinomas of the breast. J. Pathol. 226, 427-441 (2012
55. Efron B., & Tibshirani R.J. An Introduction to the Bootstrap (Chapman, & Hall, 1993