1. Expression of kinase genes in primary hyperparathyroidism; Adenoma versus hyperplastic parathyroid tissue Pinhas P. Schachter1 M.D., Suhail Ayesh2 PhD, Tamar Schneider2, Morris Laster M.D., Abraham Czerniak1 M.D. and Abraham Hochberg2

2. Background Differentiation between parathyroid hyperplasia and adenoma is difficult and based on the surgeon’s skill. Microarrays and other sophisticated research tools generate information about differential gene expression in various tissues. Exploration of genes that express differentially in one tissue will enable identification and perhaps development of new methods of preoperative or intraoperative diagnosis.

3. Methods RNA was extracted from parathyroid hyperplasia and adenoma tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes. Signals of exposure were scanned and quantified with Atlas – Image, version 2, software for digital image analysis. The program generates a color schematic comparison view and numerical data in a tabular format for further analysis.

4. Expression of kinase genes In Adenoma Parathyroid Tissue Expression of kinase genes In Adenoma Parathyroid Tissue

5. Expression of kinase genes In hyperplasia Parathyroid Tissue Expression of kinase genes In hyperplasia Parathyroid Tissue

6. The first row data format in text mode

7. The second excel format of data

8. The third access format after classefication

9. Table 1 Genes expressed in Parathyroid hyperplasia only

10. Table 2 Genes expressed in Parathyroid adenoma only

11. Table 3 Genes up regulated in Parathyroid adenoma

12. Table 4 Genes down regulated in Parathyroid adenoma

13. Table 5 Genes categories by function

14. Conclusion The ratio values that are considered significant ( 1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for angiogenesis and production of blood vessels. Genes down-regulated in parathyroid adenoma and expressed in hyperplasia are related to a decrease in apoptosis. Moreover, an interesting gene expressed only in the hyperplasia sample is increased in relation to in vivo proliferation activities

15. http://research.dfci.harvard.edu/korsmeyer/MLL.htm MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia Scott A. Armstrong1–4, Jane E. Staunton5, Lewis B. Silverman1,3,4, Rob Pieters6, Monique L. den Boer6, Mark D. Minden7, Stephen E. Sallan1,3,4, Eric S. Lander5, Todd R. Golub1,3,4,5* & Stanley J. Korsmeyer2,4,8* *These authors contributed equally to this work.

16. Abstract Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.

17. Genes that distinguish ALL from MLL. The 100 genes that are most highly correlated with the class distinction

18. Selected early lymphocyte gene expression in ALL and MLL

19. Selected HOX gene expression in ALL and MLL

20. Comparison of gene expression between ALL, Mll and AML ALL (red), MLL (blue), AML (yellow)

21. Genes that are specifically expressed in MLL, ALL or MLL

22. Classification of ALL, MLL and AML on the basis of their gene expression profile. The error rate in class prediction (y axis) is plotted against the number of genes used to build the model (x axis).