ACUTE MYELOGENOUS LEUKEMIA
most often seen in M2 AML
most often seen in AML arising from MDS
immunodeficiency, telangiectasias, progressive neurological degeneration, breast (heterozygotes have 3.9X RR)
50% Rb inactivation
60% P53 mutation
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%)
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.
chromosome 5: -5, 5q-
chromosome 7: -7, 7q-
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
Rb gene inactivation
RENAL CELL CARCINOMA
3p14 deletion...........VHL gene
Rb gene inactivation
ALVEOLAR RHABDOMYOSARCOMA t(2;13)
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.
germline P53 mutation
carriers have 50% chance of cancer diagnosis by age 30 & 95% chance by age 65. Cancers include: Breast, childhood sarcoma, etc.