Protein correlates of genetic alterations

Question 1

beta-catenin is a product of what genetic alteration? What tumours has abberant staining?

Answer 1

Wnt signaling pathway, either by somatic mutations in the CTNNB1 gene encoding beta-catenin, or as a result of germline mutation in APC (in famililal adenomatous polyposis).

Beta catenin normally in the cell membrane, coordinates cell-cell adhesion and gene transcription, abnormally accumulates in the cytoplasm and nucleus. Upon Wnt activation, β catenin is translocated from membrane (where it interacts with E-cadherin) to cytoplasm and nucleus, where it interacts with transcriptional activators.

IPx for beta-catenin shows abberant nuclear staining in desmoid fibromatosis, fibroblastic, myofibroblastic tumours including solitary fibrous tumours, low grade myofibroblastic sarcoma

Question 2

What are MDM2 and CDK4? what is it used for?

Answer 2

Used to differentiate well-differentiated liposarcoma from benign lipomas, and dedifferentiated liposarcoma from pleomorphic and spindle cell sarcomas. Well-differentiated liposarc (aka atypical lipomatous tumour) and dedifferentiated liposarcoma are characterised by ring and giant marker chromosomes derived from amplified material from chromosomes 12q13~15. Ammplication results in overexpresson of MDM2 and CDK4.. MPNST and myofibrosarc, rhabdomyosarc may also express MDM2.

Question 3

What is INI1?

Answer 3

AKA SNF5 and SMARCB1, members of the SWI/SNF multisubunit chromatin remodelling complex. INI1 is expressed in nuclei of normal cells. Biallelic inactivation of SMARCB1 (loss of staining) is a defining feature of rhabdoid tumour of infancy. Other tumours with loss of staining epithelioid sarcomas.

Question 4

Which soft tissue tumour is associated with ALK protein?

Answer 4

ALK - inflammatory myofibroblastic tumour Others - anaplastic large-cell lymphoma, pulmonary AdenoCa, MPNST, alveolar rhabdomyosarcoma, neuroblastoma

Question 5

Which soft tissue tumour is associated with BCOR protein?

Answer 5

BCOR-CCNB3 sarcoma, BCOR-MAML3 sarcoma others primitive myxoid mesenchymal tumour of infancy, round cell sarcomas with BCOR internal tandem duplications Round cell sarcomas with YWHAE-NUTM2B

Question 6

Which soft tissue tumour is associated with CAMTA1 protein?

Answer 6

epithelioid hemangioendothelioma

Question 7

Which soft tissue tumour is associated with CCNB3 protein?

Answer 7

BCOR-CCNB3 sarcoma

Question 8

Which soft tissue tumour is associated with ERG?

Answer 8

small subset of Ewing, other vascular tumours, prostatic adenoca, AML

Question 9

Which soft tissue tumour is associated with FLI1?

Answer 9

Ewing Sarcoma, vascular tumours

Question 10

Which soft tissue tumour is associated with FOSB?

Answer 10

pseudomyogenic hemangioendothelioma, subset of epithelioid hemangioma

Question 11

Which soft tissue tumour is associated with ROS1?

Answer 11

inflammatory myofibroblastic tumour (small subset), pulmonary adenoCa

Question 12

Which soft tissue tumour is associated with STAT6?

Answer 12

Solitary fibrous tumour, dedifferentiated liposarcoma

Question 13

Which soft tissue tumour is associated with TFE3?

Answer 13

Alveolar soft part, xp11 translocation RCC, PEcoma, epithelioid hemangioendothelioma

Question 14

Which soft tissue tumour is associated wit4?h DOG1?

Answer 14

GIST

Question 15

Which soft tissue tumour is associated with ETV4?

Answer 15

CIC-DUX4 sarcoma

Question 16

Which soft tissue tumour is associated with MUC4?

Answer 16

Low grade fibromyxoid sarcoma Sclerosing epithelioid fibrosarcoma

Question 17

Which soft tissue tumour is associated with NKX2-2?

Answer 17

Ewing Sarcoma

Question 18

Which soft tissue tumour is associated with TLE1?

Answer 18

Synovial sarcoma