Chapter 46 : Use of Molecular Biology Methods on Tissues

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Use of Molecular Biology Methods on Tissues, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815905/9781555813642_Chap46-1.gif /docserver/preview/fulltext/10.1128/9781555815905/9781555813642_Chap46-2.gif


This chapter provides an overview of several examples of molecular biology applications in this rapidly advancing field. Not all present biomarkers can be detected in tissues that are routinely available in pathology laboratories. There is an ongoing effort to adapt techniques that work well with fresh, unfixed tissues to specimens such as formalin-fixed paraffin-embedded needle biopsy material and cytology smear material. Ligase chain reaction and similar techniques are presently used for the detection of microorganisms in tissues by labeling the oligonucleotides with organism-specific sequences. This process can also be used for detection and quantitation of the expression of specific genes in tissues. The study of familial adenomatous polyposis has demonstrated the presence of adenomatous polyposis coli gene mutations in 5q21. The study of molecular pathways of carcinogenesis has highlighted various molecules that are now therapeutic targets. A relatively simple method of examining hundreds of tissue sections in one experiment is the use of tissue microarrays (TMAs). PCR-based methodologies with the advantage of using fresh, frozen, or formalin-fixed tissues or cells are faster and less labor-intensive and have become the first-line methods in clinical laboratories for clonality testing. The majority of lymphomas and leukemias can be further classified by their characteristic chromosomal lesions. Similar to those associated with hematopoietic malignancies, most genetic abnormalities associated with soft-tissue tumors are chromosomal translocations resulting in novel fusion proteins.

Citation: Setty S, Chang C, Kajdacsy-Balla A. 2006. Use of Molecular Biology Methods on Tissues, p 403-407. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch46

Key Concept Ranking

B-cell Chronic Lymphocytic Leukemia
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Anderson, J.,, T. Gordon,, A. McManus,, T. Mapp,, S. Gould,, A. Kelsey,, H. McDowell,, R. Pinkerton,, J. Shipley,, K. Pritchard-Jones,U.K. Children’s Cancer Study Group, and the U. K. Cancer Cytogenetics Group. 2001. Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome? Br. J. Cancer 85:831835.
2. Bagg, A. 2003. Clinical applications of molecular genetic testing in hematologic malignancies: advantages and limitations. Hum. Pathol. 34:352358.
3. Bridge, J. A.,, J. Liu,, V. Weibolt,, K. S. Baker,, D. Perry,, R. Kruger,, S. Qualman,, F. Barr,, P. Sorensen,, T. Triche, and , R. Suijkerbuijk. 2000. Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study. Genes Chromosomes Cancer 27:337344.
4. Chang, C. C.,, C. Bredeson,, M. Juckett,, B. Logan, and , C. A. Keever-Taylor. 2003. Tumor load in patients with follicular lymphoma post stem cell transplantation may correlate with clinical course. Bone Marrow Transplant. 32:287291.
5. Chang, C. C., and , V. B. Shidham. 2003. Molecular genetics of pediatric soft tissue tumors: clinical application. J. Mol. Diagn. 5:143154.
6. Dazzi, F.,, R. M. Szydlo, and , J. M. Goldman. 1999. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp. Hematol. 27:14771486.
7. Gilliland, D. G., and , J. D. Griffin. 2002. The roles of FLT3 in hematopoiesis and leukemia. Blood 100:15321542.
8. Grody, W. W.,, G. R. Cutting,, K. W. Klinger,, C. S. Richards,, M. S. Watson, and , R. J. Desnick. 2001. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet. Med. 3:149154.
9. Kononen, J.,, L. Bubendorf,, A. Kallioniemi,, M. Barlund,, P. Schraml,, S. Leighton,, J. Torhorst,, M. J. Mihatsch,, G. Sauter, and , O. P. Kallioniemi. 1998. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4:844847.
10. Ladanyi, M.,, W. C. Chan,, T. J. Triche, and , W. L. Gerald. 2001. Expression profiling of human tumors: the end of surgical pathology? J. Mol. Diagn. 3:9297.
11. Lin, F.,, F. van Rhee,, J. M. Goldman, and , N. C. Cross. 1996. Kinetics of increasing BCR-ABL transcript numbers in chronic myeloid leukemia patients who relapse after bone marrow transplantation. Blood 87:44734478.
12. Malkin, D.,, F. P. Li,, L. C. Strong,, J. F. Fraumeni, Jr.,, C. E. Nelson,, D. H. Kim,, J. Kassel,, M. A. Gryka,, F. Z. Bischoff, and , M. A. Tainsky. 1990. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:12331238.
13. Medeiros, L. J., and , J. Carr. 1999. Overview of the role of molecular methods in the diagnosis of malignant lymphomas. Arch. Pathol. Lab. Med. 123:11891207.
14. Munoz, N., F., X. Bosch,, S. de Sanjose,, R. Herrero,, X. Castellsague,, K. V. Shah,, P. J. Snijders,, C. J. Meijer, and the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. 2003. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N. Engl. J. Med. 348:518527.
15. Murray, G., and , S. Curran (ed.). 2005. Laser Capture Microdissection Methods and Protocols. Humana Press, Towata, N.J.
16. Nathanson, K. N.,, R. Wooster, and , B. L. Weber. 2001. Breast cancer genetics: what we know and what we need. Nat. Med. 7:552556.
17. Park, K.,, J. Kim,, S. Lim,, S. Han, and , J. Y. Lee. 2003. Comparing fluorescence in situ hybridization methods to determine the HER-2/neu status in primary breast carcinoma using tissue microarray. Mod. Pathol. 16:937943.
18. Rassenti, L. Z.,, L. Huynh,, T. L. Toy,, L. Chen,, M. J. Keating,, J. G. Gribben,, D. S. Neuberg,, I. W. Flinn,, K. R. Rai,, J. C. Byrd,, N. E. Kay,, A. Greaves,, A. Weiss, and , T. J. Kipps. 2004. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N. Engl. J. Med. 351:893901.
19. Resnick, R. M.,, M. T. Cornelissen,, D. K. Wright,, G. H. Eichinger,, H. S. Fox,, J. ter Schegget, and , M. M. Manos. 1990. Detection and typing of human papillomavirus in archival cervical specimens by DNA amplification with consensus primers. J. Natl. Cancer Inst. 82:14771484.
20. Slamon, D. J.,, W. Godolphin,, L. A. Jones,, J. A. Holt,, S. G. Wong,, D. E. Keith,, W. J. Levin,, S. G. Stuart,, J. Udove, and , A. Ullrich. 1989. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707712.
21. Solomon, D., and , M. Schiffman. 2004. Have we resolved how to triage equivocal cervical cytology? J. Nat. Cancer Inst. 96:250251.
22. Sorensen, P. H.,, J. C. Lynch,, S. J. Qualman,, R. Tirabosco,, J. F. Lim,, H. M. Maurer,, J. A. Bridge,, W. M. Crist,, T. J. Triche, and , F. G. Barr. 2002. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children’s oncology group. J. Clin. Oncol. 20:26722679.
23. Tanner, M.,, D. Gancberg,, A. Di Leo,, D. Larsimont,, G. Rouas,, M. J. Piccart, and , J. Isola. 2000. Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am. J. Pathol. 157:14671472.
24. van de Vijver, M. J.,, Y. D. He,, L. J. van’t Veer,, H. Dai,, A. A. Hart,, D. W. Voskuil,, G. J. Schreiber,, J. L. Peterse,, C. Roberts,, M. J. Marton,, M. Parrish,, D. Atsma,, A. Witteveen,, A. Glas,, L. Delahaye,, T. van der Velde,, H. Bartelink,, S. Rodenhuis,, E. T. Rutgers,, S. H. Friend, and , R. Bernards. 2002. A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 347:19992009.


Generic image for table

Correlation of genetic lesions and immunohistochemical (IHC) markers

Citation: Setty S, Chang C, Kajdacsy-Balla A. 2006. Use of Molecular Biology Methods on Tissues, p 403-407. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch46

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error