Principles of Molecular Pathology
This is a very nice, concise review of the field of molecular pathology, a field that is still considered "new" because it requires training in several fields, including pathology, molecular methods, genetics, infectious disease, and tumor biology. The book provides readers with all of the relevant background in the first chapters so that specialists and nonspecialists alike can understand the later chapters. It can be read from cover to cover or used as a reference text on an "as-needed" basis. Considering the diversity of molecular pathology, the book is relatively short, 333 pages, but it provides a comprehensive review of the field. I particularly liked how each chapter highlighted all of the salient points of the subject material and then went on to illustrate many of the exceptions.
The book comprises 11 chapters. The first four are introductory chapters, including "Basic Concepts", "Genetic Inheritance", "Mutation", and "Inherited Disorders". They start with the structure of DNA and move on to gene structure and expression. Chapter 2 describes the basic forms of Mendelian and non-Mendelian inheritance, multifactorial disease, Bayesian risk calculation, and Hardy-Weinberg equilibrium. Chapter 3 describes all forms of mutation and provides examples ranging from simple point mutations to more complex chromosomal rearrangements. The next chapter describes all types of molecular methods from Southern blot analysis to microarray technology. This comprehensive chapter would further benefit from more discussion of comparative genome hybridization and microarrays in future editions. Two other points that could be added are the use of LightCycler for quantitative analyses in addition to TaqMan and denaturing HPLC as a scanning method. It would also be beneficial to include the sensitivity of detection for each of the scanning methods to future editions of the book. Of course, by then, some of these will be pass and other techniques will take the forefront as novel techniques.
Chapter 5 describes various inherited disorders that are now tested for in molecular pathology laboratories as well as genetics laboratories, including classic diseases such as cystic fibrosis and hemochromatosis. Mitochondrial diseases and disorders tested in newborn-screening laboratories are also covered. Chapters 6 and 7 describe the classification of tumor genes and the known familial cancer syndromes. Chapter 8 provides an extensive discussion of the rapidly evolving field of the molecular bases of hematologic malignancies. Certainly, in the next edition of this book this chapter will look very different, but as it stands, it gives a comprehensive overview of the current state of knowledge governing rearrangements in leukemias and lymphomas. Chapter 9 covers the field of pharmacogenetics, which will also likely be very different in the very near future. Chapter 10 gives a nice overview of identity testing and its use in the laboratory, and lastly, chapter 11 provides a review of molecular techniques and interpretation of results from human immunodeficiency virus and hepatitis C virus testing. Both of these tests have multiple means for detection, and this final chapter nicely outlines the information gained from each type of test when used clinically.
In conclusion, this book would make a welcome and timely addition to laboratory libraries because it covers a wide field in an easy-to-read manner. It is also a useful text for those studying for Board exams because all of the major topics that come to mind are nicely covered. Several other texts relating to molecular pathology read more like laboratory manuals, but Dr. Killeens book covers much of the background necessary to understand the topic in addition to the overview of the molecular methods. The book also provides web site addresses that contain important, more comprehensive information for the reader who desires to learn more, as well as the latest professional guidelines addressing testing and reporting/use of information. These inclusions alone provide a great service to and an excellent reference for molecular pathologists.
Martine Roudier, MD, PhD
Killeen AA. Principles of Molecular Pathology. Totowa, NJ: Humana Press, 2003, 344 pp, $120.
"Happy is he who gets to know the reasons for things." Virgil, 70-19 BC
For a surgical practicing pathologist like myself, born before the 1970s, the book Principles of Molecular Pathology is an illuminating guide to understanding the powerful tools of molecular biology and how these tools can be used in the practice of pathology.
When I started to extract RNA from tissue a few years ago, a colleague told me that molecular biology is not like cooking. We do not see any of the materials during the process, but, at the end, the tangible results are there, striking, having appeared from an invisible world. I found myself confronted with a poignant contradiction: I had chosen pathology as my career because the disease was visible; and with a lot of confidence (if not happiness) I could, in most cases, live with a peaceful mind even in the face of having made a dreadful diagnosis. The microscopic features of diseases were the symptoms and signs of a patient's disease leading to a well-defined diagnosis. Nowadays, those signature features can be invisiblemolecular. Cancer can be characterized and is beginning to be understood at the molecular level. The transition from cellular to molecular in the pathologist's practice was needed. Principles of Molecular Pathology clearly testifies for the first time to the values and broad applications of molecular pathology in medicine.
The book of fewer than 350 pages is so well written that a less molecularly oriented pathologist can read the entire text within only 30 hours. The book is small (half an A4 format) and compact with a font and an overall layout of text and essential schematics that make it a pleasure to peruse. One of its best features is an extremely lucid text, without repetition. The text covers topics chosen to provide a broad overview of the subject. Concise basic concepts of molecular biology and genetics are followed by an accurate description of the most commonly and currently used analytic methods. One chapter explains the acquired genetic abnormalities that underlie inherited disorders. Two essential chapters describe, masterfully, the important genetic determinants of human malignancies, acquired and hereditary. These 2 chapters are beautifully crafted and provide the reader with lasting enlightenment. One entire chapter is dedicated to the molecular understanding of myeloid and lymphoid malignancies, which reads like a police novel by pathologists who excel in the morphologic and immunologic diagnosis of hematologic disorders. Chapters on pharmacogenetics and identity testing emphasize the current importance and futuristic implications of these areas in clinical practice. Finally, the current application of molecular methods is described in the detection of a few major bacterial and viral infections.
This is a wonderful and unique book that should be purchased by a wide readership, including residents and fellows in laboratory medicine and pathology, practicing pathologists desiring to easily understand the current transition of their practice, and specialized research pathologists interested in broadening their general knowledge in the powerful tool of molecular pathology
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