Investigative pathology: leading the post-genomic revolution

The completion of the Human Genome Project and the development of genome-based technologies over the past decade have set the stage for a new era of personalized medicine. By all rights, molecularly trained investigative pathologists should be leading this revolution. Singularly well suited for this work, molecular pathologists have the rare ability to wed genomic tools with unique diagnostic skills and tissue-based pathology techniques for integrated diagnosis of human disease. However, the number of pathologists with expertise in genome-based research has remained relatively low due to outdated training methods and a reluctance among some traditional pathologists to embrace new technologies. Moreover, because budding pathologists may not appreciate the vast selection of jobs available to them, they often end up choosing jobs that focus almost entirely on routine diagnosis rather than new frontiers in molecular pathology. This review calls for changes aimed at rectifying these troubling trends to ensure that pathology continues to guide patient care in a post-genomic era.

[1]  P. Jänne Challenges of detecting EGFR T790M in gefitinib/erlotinib-resistant tumours. , 2008, Lung cancer.

[2]  M. Cronin,et al.  Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  E. Mardis The $1,000 genome, the $100,000 analysis? , 2010, Genome Medicine.

[4]  R. Drapkin,et al.  New insights into the pathogenesis of serous ovarian cancer and its clinical impact. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  S. Aparicio,et al.  Does massively parallel DNA resequencing signify the end of histopathology as we know it? , 2010, The Journal of pathology.

[6]  Ryan D. Morin,et al.  Mutation of FOXL2 in granulosa-cell tumors of the ovary. , 2009, The New England journal of medicine.

[7]  Robert B. Hartlage,et al.  This PDF file includes: Materials and Methods , 2009 .

[8]  A. Ashworth,et al.  Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas , 2010, The Journal of pathology.

[9]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[10]  Andrew Menzies,et al.  The patterns and dynamics of genomic instability in metastatic pancreatic cancer , 2010, Nature.

[11]  Lee T. Sam,et al.  Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer. , 2011, Genome research.

[12]  Ryan D. Morin,et al.  Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution , 2009, Nature.

[13]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[14]  Emily H Turner,et al.  Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome , 2010, Nature Genetics.

[15]  P. Stankiewicz,et al.  Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. , 2010, The New England journal of medicine.

[16]  P. Shannon,et al.  Analysis of Genetic Inheritance in a Family Quartet by Whole-Genome Sequencing , 2010, Science.

[17]  R. Drapkin,et al.  The distal fallopian tube: a new model for pelvic serous carcinogenesis , 2007, Current opinion in obstetrics & gynecology.

[18]  P. Meltzer,et al.  High frequency of BRAF mutations in nevi , 2003, Nature Genetics.

[19]  M. Meyerson,et al.  A Rapid and Sensitive Enzymatic Method for Epidermal Growth Factor Receptor Mutation Screening , 2006, Clinical Cancer Research.

[20]  A. Ashworth,et al.  Genetic Interactions in Cancer Progression and Treatment , 2011, Cell.

[21]  Richard A. Moore,et al.  ARID1A mutations in endometriosis-associated ovarian carcinomas. , 2010, The New England journal of medicine.

[22]  D. Hayes,et al.  Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.