Molecular Pathology in Clinical Practice

1 Basics of Molecular Biology .................................................................................... 1
Deborah Ann Payne
2 Molecular Pathology Methods ................................................................................ 19
D. Hunter Best , Shale A. Dames , Whitney Wooderchak- Donahue ,
Tracey Lewis , Kelli L. Sumner , Cecily P. Vaughn , Rong Mao ,
and Daniel H. Farkas
Section I Genetics
3 Genetic Counseling .................................................................................................. 55
Christine E. Miller
4 Pedigree Analysis and Risk Assessment ................................................................. 63
Patti Krautscheid and Danielle LaGrave
5 Bayesian Analysis ..................................................................................................... 77
Robert B. Wilson and Shuji Ogino
6 Intellectual Disability and Developmental Delay: Cytogenetic Testing .............. 91
Guangyu Gu , Reha Toydemir , and Sarah T. South
7 Developmental Delay: Gene Testing ....................................................................... 101
Christin D. Collins , Monica J. Basehore , Kristen J. Champion ,
and Michael J. Friez
8 Congenital Disorders of Glycosylation ................................................................... 121
Melanie A. Jones and Madhuri R. Hegde
9 Neuromuscular Diseases .......................................................................................... 127
Thomas W. Prior
10 Mitochondrial Disorders ......................................................................................... 139
Renkui Bai and Jaimie D. Higgs
11 Metabolic Disorders ................................................................................................. 161
Lisa Edelmann , Yaping Yang , Amy C. Yang , and Ruth Kornreich
12 Fibroblast Growth Factor Receptor and Related Skeletal Disorders ................. 177
Steven Sperber and Elaine Spector
13 Cystic Fibrosis .......................................................................................................... 189
Lora J. H. Bean and V. M. Pratt
14 Deafness .................................................................................................................... 197
A. Eliot Shearer , Robert W. Eppsteiner , and Richard J. H. Smith
Contents

Molecular Pathology in Clinical Practice
15 Coagulation Disorders ............................................................................................. 203
Rajiv K. Pruthi , Michelle L. Kluge , and Aneel A. Ashrani
16 Hematologic Disorders: Hemochromatosis, Hemoglobinopathies,
and Rh Incompatibility............................................................................................ 225
Daniel B. Bellissimo and Archana Agarwal
17 Cardiovascular Disease............................................................................................ 239
Samantha M. Baxter and Birgit H. Funke
18 Neurodegenerative Disorders .................................................................................. 261
Maria Martinez-Lage
19 Polycystic Kidney Disease ....................................................................................... 277
Adrian Y. Tan , Jon Blumenfeld , and Hanna Rennert
20 Host Factor Pharmacogenetics for Treatment of Infectious Diseases ................. 291
Patricia R. Slev and David R. Hillyard
21 Pharmacogenetics .................................................................................................... 301
Stuart A. Scott and Elaine Lyon
Section II Inherited Cancers
22 Inherited Breast Cancer .......................................................................................... 315
Rachel Michaelson-Cohen , Rachel Beeri , Eliahu Golomb ,
and Ephrat Levy-Lahad
23 Familial Adenomatous Polyposis and Turcot
and Peutz–Jeghers Syndromes................................................................................ 329
Kandelaria M. Rumilla
24 Hereditary Nonpolyposis Colorectal Cancer and Lynch Syndrome ................... 339
James P. Grenert
25 Multiple Endocrine Neoplasia Syndromes ............................................................ 351
Barbara A. Zehnbauer
26 Von Hippel-Lindau Disease ..................................................................................... 365
Catherine A. Stolle
27 Hereditary Skin Cancer........................................................................................... 369
Dani Bercovich and Inbal Kedar
28 Li-Fraumeni Syndrome ........................................................................................... 377
Arupa Ganguly and Zhao Chen
29 Retinoblastoma ......................................................................................................... 385
Arupa Ganguly and Zhao Chen
30 Hereditary Paraganglioma and Pheochromocytoma ........................................... 393
Fang-Yuan Li and Lee-Jun C. Wong
Section III Solid Tumors
31 Colorectal Cancer .................................................................................................... 403
Antonia R. Sepulveda , Deqin Ma , Kathryn C. Behling , and Helen Fernandes
32 Lung Cancer ............................................................................................................. 419
Dara L. Aisner , Robert C. Doebele , Marileila Varella- Garcia ,
and Wilbur A. Franklin
Contents

xi
33 Breast Cancer ........................................................................................................... 433
Carolyn Mies
34 Urothelial Carcinoma .............................................................................................. 447
Kevin C. Halling
35 Prostate Cancer ........................................................................................................ 453
Priti Lal
36 Thyroid Cancer ........................................................................................................ 471
Marina N. Nikiforova and Yuri E. Nikiforov
37 Sarcomas and Related Mesenchymal Tumors ....................................................... 487
Giovanni Tallini , Dario de Biase , and Pei Hui
38 Gliomas ..................................................................................................................... 507
Ehud Lavi
39 Molecular Detection of Circulating Tumor Cells and Cell-Free
Nucleic Acids ............................................................................................................ 515
Nirali M. Patel and Karen Kaul
Section IV Neoplastic Hematopathology
40 Acute Myeloid Leukemia......................................................................................... 527
David Grimwade , Steven Knapper , and Krzysztof Mrózek
41 Acute Lymphoblastic Leukemia ............................................................................. 561
Andrea Biondi , Carlos Alberto Scrideli , and Giovanni Cazzaniga
42 B-Cell Malignancies ................................................................................................. 579
Jennifer B. Dunlap , Guang Fan , Nicky Leeborg , and Rita M. Braziel
43 T-Cell Lymphomas ................................................................................................... 603
Jason D. Merker and Daniel A. Arber
44 Myeloproliferative Neoplasms and Myelodysplastic Syndromes ........................ 615
Albert K. Ho and Daniel M. Jones
Section V Infectious Diseases
45 Human Immunodeficiency Virus Type 1 ............................................................... 629
Angela M. Caliendo and Colleen S. Kraft
46 Hepatitis B and C Viruses ....................................................................................... 641
Frederick S. Nolte
47 Viral Infections in Transplant Recipients .............................................................. 659
Raymund R. Razonable and Randall T. Hayden
48 Viral Infections of the Central Nervous System .................................................... 681
Duane W. Newton and Christine C. Ginocchio
49 Bacterial Infections .................................................................................................. 695
Kevin Alby and Melissa B. Miller
50 Gastrointestinal Infections ...................................................................................... 707
Eileen M. Burd and Benjamin H. Hinrichs
51 Sexually Transmitted Diseases ................................................................................ 735
Jeanne A. Jordan
Contents

xii
52 Respiratory Infections ............................................................................................. 755
Christine C. Ginocchio
53 Mycobacterial Infections ......................................................................................... 779
Betty A. Forbes
Section VI Identity Testing
54 Forensic DNA Typing .............................................................................................. 793
Victor W. Weedn and David R. Foran
55 Parentage and Relationship Testing ....................................................................... 811
Robert W. Allen and Herbert F. Polesky
56 Chimerism Testing in Allogeneic Hematopoietic
Stem Cell Transplantation....................................................................................... 823
Vivianna M. Van Deerlin and Ran Reshef
57 Specimen Identification Through DNA Analysis .................................................. 849
Gregary Bocsi , Andrew Ricci , Gregory J. Tsongalis , and Vivianna M. Van Deerlin
Section VII HLA Typing
58 Molecular HLA Typing ........................................................................................... 867
Malek Kamoun , Jill A. Hollenbach , Steven J. Mack , and Thomas M. Williams
Section VIII Evolving Clinical Molecular Technologies
59 Next-Generation Sequencing: Principles for Clinical Application ...................... 889
Karl V. Voelkerding , Emily M. Coonrod , Jacob D. Durtschi ,
and Rebecca L. Margraf
60 Next-Generation Sequencing for the Analysis of Cancer Specimens .................. 911
John D. Pfeifer
61 Clinical Applications of Proteomics ....................................................................... 933
Delphine Rolland and Kojo S. J. Elenitoba-Johnson
Section IX Laboratory Management
62 Molecular Pathology Laboratory Management .................................................... 945
Hanna Rennert and Debra G.B. Leonard
Index .................................................................................................................................. 975

Interpretation
Based on identifi ed CYP2C19 genotype, individuals typically
are categorized as extensive ( *1/*1 ), intermediate (e.g., *1 / *2 ,
*1/*3 ), or poor (e.g., *2 / *2 , *2 / *3 ) metabolizers [ 20 ]. The frequencies
of CYP2C19 poor metabolizers are 2–5 % of
Caucasians and African Americans and approximately 15 %
of Asians [ 23 , 26 ]. Additionally, individuals who have at least
one copy of the CYP2C19*17 allele often are categorized as
ultrarapid metabolizers (e.g., *17 / *17 ). However, given that
*17 is unable to completely compensate for the *2 loss-offunction
allele [ 27 ], *2 / *17 compound heterozygotes can be
classifi ed as intermediate metabolizers, although some laboratories
may report the predicted phenotype for this genotype as
“unknown” or “indeterminate.”