ACUTE MYELOGENOUS LEUKEMIA t(9;22) Philadelphia chromosome t(8;21) most often seen in M2 AML t(9;11) most often seen in AML arising from MDS _________________________________ ATAXIA-TEANGIECTASIA AT gene immunodeficiency, telangiectasias, progressive neurological degeneration, breast (heterozygotes have 3.9X RR) _________________________________ BLADDER C-ras mutation 50% Rb inactivation 60% P53 mutation _________________________________ BREAST brca-1 (17q21) breast, ovary, colon, ?prostate brca-2 (13q12-q13) breast, male breast _________________________________ CHRONIC LYMPHOCYTIC LEUKEMIA 13q (55% of cases) [DBM tumor suppressor gene] deletion in 11q (18%) trisomy of 12q (16%) deletion in 17p (7%) deletion in 6q (6%) _________________________________ COLON APC gene inactivation _________________________________ GI STROMAL TUMOR (GIST) c-kit: GIST expresses the c-kit oncogene (CD117), a tyrosine kinase. _________________________________ HEAD & NECK CANCERS EGF receptor over expression is seeen in up to 90% of cases. P53 mutation is seen in 50-70% of cases HPV-16 genome is detected in a fraction of those that do not have a P53 mutation. Most of the HPV positive cases are HPV-16. Oropharynx cancer is the most frequently encountered head & neck cancer that is positive for HPV. _________________________________ MELANOMA P16(INK4) _________________________________ MYELDYSPLASTIC SYNDROME chromosome 5: -5, 5q- chromosome 7: -7, 7q- trisomy 8 _________________________________ NON-HODGKINS LYMPHOMA t(14;18): results in deregulation & increased expression of bcl-2 gene on chromosome 18 Seen in FOLLICULAR NHL Seen also in DIFFUSE LARGE B CELL LYMPHOMA (30% of cases) t(11;14): the bcl-1 locus containing the PRAD-1 or cyclin D1 gene on chromosome 11 is placed in proximity to the immune globulin heavy chain gene on chromosome 14. Seen in MANTLE CELL LYMPHOMA t(8;14): seen in BURKITTS LYMPHOMA. c-myc is translocated from chromosome 8 to the proximity of the immune globulin gene promoters on chromosome 14, 2, or 22. This results in c-myc degregulation & activation. t(3;14): bcl-6 gene on chromosome 3 is involved in this translocation. Note that this gene could translocate into any of the light or heavy chains! Seen in DIFFUSE LARGE B-CELL LYMPHOMA b(30-35% of SIg+ cases) t(2;5): Seen in T-CELL ANAPLASTIC LARGE CELL NHL. Involves ALK gene translocation. t(9;14): Seen in LYMPHOPLASMACYTIC LYMPHOMA. Involves PAX-5 translocation _________________________________ OSTEOSARCOMA Rb gene inactivation _________________________________ RENAL CELL CARCINOMA 3p14 deletion...........VHL gene _________________________________ RETINOBLASTOMA Rb gene inactivation _________________________________ SARCOMA SYNOVIAL t(X;18) ALVEOLAR RHABDOMYOSARCOMA t(2;13) _________________________________ TESTICULAR i(12p).........found on all histologic types of germ cell tumors.This marker has been helpful in determining the germ cell origin of teratomas in malignant transformations & in mediastinal tumors. _________________________________ LI-FRAUMERNI SYNDROME germline P53 mutation carriers have 50% chance of cancer diagnosis by age 30 & 95% chance by age 65. Cancers include: Breast, childhood sarcoma, etc. _________________________________ |