Molecular Associations Flashcards
What chromosome is Ig kappa located on?
Chromosome 2. Associated with B cell lymphomas (follicular, mantle cell, lymphoplasmacytic, Burkitt, myeloma).
What chromosome is Ig lambda located on?
Chromosome 22. Associated with B cell lymphomas (follicular, mantle cell, lymphoplasmacytic, Burkitt, myeloma).
What chromosome is IgH located on?
Chromosome 14. Associated with B cell lymphomas (follicular, mantle cell, lymphoplasmacytic, Burkitt, myeloma).
What chromosome is TCR alpha and delta located on?
Chromosome 14. T cell leukemia/lymphoma
What chromosome is TCR beta and gamma located on?
7q (TCR beta); 7p (TCR gamma). T cell leukemia/lymphoma
What chromosome is c-Myc located on? Which lymphoma is it associated with?
8; Burkitt lymphoma
What chromosome is n-Myc located on? Which tumor is it associated with?
2; Neuroblastoma
What chromosome is Bcl-2 on? What lymphoma(s) are associated with Bcl-2?
18; Follicular lymphoma; Diffuse large B-cell lymphoma
What chromosome is p53 located on?
17p; mutated in many sporadic tumors (mutation associated with overexpression) and in Li-Fraumeni syndrome
What chromosome(s) is BCR-ABL associated with? Which lymphoma(s) is BCR-ABL associated with?
9 (ABL); 22 (BCR); CML Ph p210>p230»p190; B-ALL Ph p190»p210* * the presence of p210 in a patient with acute leukemia should prompt consideration of CML in blast crisis.
What chromosome is WT1 located on? Which tumors?
11p13; Wilms tumor 11p13 mutation; Desmoplastic small round cell tumor t(11;22)/EWS-WT1
What chromosome is EWS located on? Which tumors?
22; Ewing sarcoma t(11;22)/EWS-FLI1; Desmoplastic small round cell tumor t(11;22)/EWS-WT1; Clear cell sarcoma; Angiomatoid Fibrous Histiocytoma: identical translocation t(12;22)/EWS-ATF1; Myxoid Liposarcoma t(12;22)/EWS-CHOP; Extraskeletal myxoid chondrosarcoma t(9;22)/EWS-CHN/TEC
What chromosome is ALK located on? Which tumors?
2; ALCL t(2;5)/NMP-ALK (80%); t(1;2)/TPM3-ALK (10%); Inflammatory myofibroblastic tumor- various translocations of 2p23; Lung adenocarcinoma EML4-ALK
What chromosome is ETV6 (TEL) located on? Which tumors?
12; Precursor B-ALL t(12;21)/ETV6-AML1; Myeloid neoplasms with PDGFRB rearrangement (CMML with eosinophilia) t(5;12)/ETV6-PDGFRB; Infantile fibrosarcoma; Congenital mesoblastic nephroma; Secretory CA of the breast; Mammary analogue secretory carcinoma of salivary glands: Identical translocation t(12;15)/ETV6-NTRK3
What chromosome is TFE3 located on? Which tumors?
Xp11.2; Alveolar soft parts sarcoma; RCC with Xp11.2: identical translocation t(X;17)/ASPL-TFE3; PEComas
What chromosome is INI1 (hSNF5/BAF47) located on? Which tumors?
22q11; Rhabdoid tumors (renal and extra-renal rhabdoid tumors, atypical teratoid/rhabdoid tumor of the brain). Others: epithelioid sarcoma, myoepithelial carcinoma of soft tissue, medullary carcinoma of kidney
What chromosome is FUS (TLS) located on? Which tumors?
16p11; Myxoid liposarcoma t(12;16)/FUS-CHOP; Low grade fibromyxoid sarcoma (Evans tumor) t(7;16)/FUS-CREB3L2; Angiomatoid Fibrous Histiocytoma t(12;16)/FUS-ATF1
What chromosome is MLL located on? Which tumors?
11q23; AML (M5), AML s/p topo II therapy, B-ALL
What chromosome is VHL located on? Which tumors?
3p; Sporadic and hereditary clear cell RCC, von Hippel Lindau syndrome
Chromosomal mutation for Desmoplastic small round cell tumor
t(11;22)/EWS-WT1
Chromosomal mutation for Wilms tumor
11p13 mutation. WT1
Chromosomal mutation for Ewing sarcoma
t(11;22)/EWS-FLI1, EWS is on 22, FLI1 on 11
Chromosomal mutation for Desmoplastic small round cell tumor
t(11;22)/EWS-WT1, EWS is on 22, WT1 on 11
Chromosomal mutation for Clear cell sarcoma & Angiomatoid Fibrous Histiocytoma
identical translocation t(12;22)/EWS-ATF1
Chromosomal mutation for Myxoid Liposarcoma
t(12;22)/EWS-CHOP
Chromosomal mutation for Extraskeletal myxoid chondrosarcoma
t(9;22)/EWS-CHN/TEC
Chromosomal mutation for Anaplastic Large Cell Lymphoma
t(2;5)/NMP-ALK (80%)t(1;2)/TPM3-ALK (10%);
Chromosomal mutation for Inflammatory myofibroblastic tumor
various translocations of 2p23, affecting ALK
Chromosomal mutation for Lung adenocarcinoma
EML4-ALK
Chromosomal mutation for Precursor B-ALL
t(12;21)/ETV6-AML1
Chromosomal mutation for Myeloid neoplasms with PDGFRB rearrangement (CMML with eosinophilia)
t(5;12)/ETV6-PDGFRB
Chromosomal mutation for: Infantile fibrosarcoma; Congenital mesoblastic nephroma; Secretory CA of the breast; Mammary analogue secretory carcinoma of salivary glands:
Identical translocation t(12;15)/ETV6-NTRK3
Xp11.2 (TFE)
Alveolar soft parts sarcoma; RCC with Xp11.2: identical translocation t(X;17)/ASPL-TFE3; PEComas
Chromosomal mutation for: Rhabdoid tumors (renal and extra-renal rhabdoid tumors, atypical teratoid/rhabdoid tumor of the brain). Others: epithelioid sarcoma, myoepithelial carcinoma of soft tissue, medullary carcinoma of kidney
22q11 (INI1)
Chromosomal mutation for Myxoid liposarcoma
t(12;16)/FUS-CHOP; FUS is on Chr16
Chromosomal mutation for Low grade fibromyxoid sarcoma (Evans tumor)
t(7;16)/FUS-CREB3L2; FUS is on Chr16
Chromosomal mutation for Angiomatoid Fibrous Histiocytoma
t(12;16)/FUS-ATF1; FUS is on Chr16
Chromosomal mutation for: AML (M5), AML s/p topo II therapy, B-ALL
11q23; MLL
Chromosomal mutation for: Sporadic and hereditary clear cell RCC, von Hippel Lindau syndrome
VHL; 3p
TK receptor: RET
10; Activating mutations: Thyroid (papillary CA, medullary CA), MEN2a, MEN2b
Inactivating mutations: Hirschsprung’s disease
TK receptor: MET
7; Papillary RCC (hereditary and occasionally sporadic)
TK receptor: KRAS
12; Pancreas, colon, lung, ovary (mucinous)
TK receptor: BRAF
7; Papillary thyroid CA, melanoma, colorectal cancer
Targeted Rx under development
TK receptor: ABL
9; CML, B-ALL (Ph+)
Targeted Rx with TK inhibitor Gleevec (Imantinib)
TK receptor: c-kit
4; GIST, melanoma, mastocytosis
Targeted Rx with TK inhibitor Gleevec (Imantinib)
TK receptor: PDGFR
4; GIST, myeloid & lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA or PDGFRB
Targeted Rx with TK inhibitor Gleevec (Imantinib)
TK receptor: EGFR
7; Mutated in some lung CA
Targeted Rx with EGFR inhibitors
TK receptor: HER2
17; Amplified in some breast CA.
Targeted Rx with Trastuzumab (Herceptin)
Cytogenetic abnormality seen in clear cell RCC?
del 3p
Cytogenetic abnormality seen in Papillary RCC?
Papillary RCCs are associated with trisomy 7, 16, and 17 and loss of the Y chromosome.
Cytogenetic abnormality seen in Chromophobe RCCs?
Chromophobe RCCs are associated with multiple monosomies. 1, 2 , 6.
What is the genetic alteration seen in most mammary analogue secretory carcinoma of salivary glands (MASC)?
ETV6-NTRK3 gene fusion, t(12;15) (p13;q25) ETV6-NTRK3 translocation. histomorphologic and immunohistochemical features reminiscent of secretory carcinoma of the breast. These tumors had features resembling both salivary acinic cell carcinoma and low-grade cystadenocarcinoma, and displaying strong similarities to breast secretory carcinoma and the authors chose the term mammary analogue secretory carcinoma of salivary glands (MASC). Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff and mucicarmine.
What is the genetic alteration seen in most mucoepidermoid carcinomas?
MECT1-MAML2
What is the genetic alteration seen in most salivary adenoid cystic carcinomas?
MYB-NFIB
What is the genetic alteration seen in most Clear cell sarcoma (malignant melanoma of soft parts) and hyalinizing clear cell carcinoma in the salivary gland
EWS-ATF1, EWSR1-ATF1 (also EWSR1-CREB1 in clear cell sarcoma )
Cylindromatosis (turban tumor syndrome), multiple familial Trichoepithelioma, and Brooke-Spiegler syndrome (a cutaneous condition characterized by multiple cystic and solid nodules appearing on the face).
CYLD gene loss is seen in trichoepitheliomas
A 34-year-old woman with a history of carotid body paraganglioma resected two years ago developed bone metastases confirmed by biopsy. She has multiple male and female family members with pheochromocytomas and neck paragangliomas. Which gene is most likely mutated?
SDHB. At least 10% of paragangliomas of the head and neck are familial. It is currently believed that 1/3 to 1/2 of carotid body paragangliomas are familial. Mutation of the succinate dehydrogenase (SDH) genes (SDHD, SDHB and SDHC) accounts for the majority (at least 70%) of the familial paraganglioma cases. Most studies demonstrate that those with SDHB mutations are more likely to have malignant paragangliomas than those with SDHC and SDHD mutations. SDHD mutations demonstrate maternal imprinting.
In HPV positive SCCs, what is the most likely explanation for the p16 staining pattern?
HPV-related inhibition of RB. p16 tumor suppressor protein is paradoxically overexpressed
in virtually all HPV+ tumors. This results from upregulation, which occurs in response to E7 viral oncoprotein-mediated functional inactivation of RB. Therefore, similar to HPV- related uterine cervix cancers, p16 immunohistochemistry can be used as a surrogate marker for the presence of high-risk HPV in these tumors. In contrast, dysregulation of p53 is mediated by E6 viral oncoprotein-mediated degradation.
what is the most common gene altered in the most common salivary gland neoplasm?
PLAG1, Pleomorphic adenoma (60% of salivary gland neoplasms). Most commonly PLAG1 gene on 8q12 followed by HMGA2 on 12q14-15.
Most common gene mutated in Pilomatrixoma?
CTNNB1 (beta catenin). Pilomatricomas consist of anucleate squamous cells (called “ghost cells”), benign viable squamous cells and multi-nucleated giant cells. The presence of calcifications is common.
Nasopharyngeal carcinoma (NPC) is an uncommon form of squamous cell carcinoma arising in the nasopharynx,The non-keratinizing forms are usually associated with —?
EBV. As opposed to SNUC, Patients with NPC frequently develop lymph node metastases which are often bilateral and classically involve the posterior cervical chain more often than other head and neck sites. These tumors are highly responsive to radiation therapy which is the mainstay of therapy with 5-year survival rates around 75-80%.
NUT midline carcinoma (NMC) cytogenetics and genetic alteration?
t(15;19), BRD4-NUT. Sinonasal mass. NUT midline carcinoma (NMC) is a recently described malignancy that is defined by balanced translocations involving the NUT (nuclear protein in testis) gene on chromosome 15q14. In approximately two thirds of cases, the translocation occurs with the BRD4 (bromodomain-containing protein 4) gene on 19p13.1, leading to a BRD4-NUT fusion oncogene. The remaining cases have a different translocation partner. NMC is an aggressive and almost uniformly lethal tumor with a propensity for early hematogenous spread. The mean patient survival time is only 9 months.
