Posted in Molecular pathology

Tumors characterized by loss of SMARCB1/INI1

SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) is a Protein Coding gene.

Tumors associated with SMARCB1 can be due to it’s complete loss, mosaic expression and reduced expression.

*TUMORS ASSOCIATED WITH COMPLETE LOSS OF SMARCB1

*TUMORS ASSOCIATED WITH MOSAIC EXPRESSION OF SMARCB1

*REDUCED EXPRESSION OF SMARCB1GROUP

Tumors characterized by SMARCB1/INI1 loss

TUMORS ASSOCIATED WITH COMPLETE LOSS OF SMARCB1

1. Atypical/Teratoid rhabdoid tumor: An atypical teratoid rhabdoid tumor (AT/RT) is a rare tumor usually diagnosed in childhood. Although usually a brain tumor, AT/RT can occur anywhere in the central nervous system (CNS), including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). Almost all tumors show complete loss of SMARCB1/INI1.

2. Epithelioid sarcoma: Epithelioid sarcoma is a type of soft tissue sarcoma that typically appears in the extremities (especially in the arms and hands). It also can develop in the main part of the body. It can affect both children and adults, but is most common in young adulthood. Complete loss of SMARCB1/INI1 is found in 70-100% cases.

3. Renal medullary carcinoma: Renal medullary carcinoma, also known as RMC, is a rare cancer of the kidney that predominantly afflicts young people of African descent who carry the sickle cell trait, sickle cell disease, or other sickle hemoglobinopathies that can cause sickling of the red blood cells.

4. Extra skeletal myxoid chondrosarcoma: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue malignancy that is distinguished from other sarcomas by its unique histology and a characteristic chromosomal translocation, typically t(9;22)(q22;q12. 2), fusing EWSR1 to NR4A3. In extraskeletal myxoid chondrosarcomas without NR4A3 fusion, tumors may harbor loss of SMARCB1 (INI1) by loss of function mutation or gene deletion. Extraskeletal myxoid chondrosarcomas without EWSR1-NR4A3 fusion may exhibit rhabdoid morphology and high grade pathological features.

5. Malignant chordoma: Chordoma is a slow growing cancer of tissue found inside the spine. Chordoma can happen anywhere along the spine. It is most often found near the tailbone (called a sacral tumor) or where the spine meets the skull (called a clival tumor). Chordoma is also called notochordal sarcoma. Pediatric chordomas are commonly associated with SMARCB1/ INI1 loss.

6. Sinonasal basaloid carcinoma: Sinonasal basaloid carcinoma occurs in relatively younger patients but over a wide age range, and shows a variable but distinctive growth pattern associated with subtle rhabdoid cells and complete loss of nuclear SMARCB1/INI1. This pattern represents a distinctive variant of sinonasal basaloid carcinoma, described as “SMARCB1(INI1)-deficient basaloid carcinoma.”

Here is mnemonic for you

TUMORS ASSOCIATED WITH MOSAIC EXPRESSION OF SMARCB1

1. Schwannomatosis- SMARCB1 mutations are found in a significant proportion of schwannomatosis patients, and an even higher proportion of rhabdoid patients. Familial schwannomatosis, which is associated with SMARCB1/INI1 loss.

2. Gastrointestinal stromal tumor (GIST)- Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that can be located in any part of the digestive system. Their most common sites are the stomach and small intestine.

3. Ossifying fibromyxoid tumor- Ossifying fibromyxoid tumor (OFMT) is a distinctive mesenchymal neoplasm of uncertain differentiation, with cords, nests, clusters and sheets of uniform ovoid cells embedded in a variable myxoid, fibromyxoid or hyalinized stroma, often with an incomplete peripheral shell of bone

REDUCED EXPRESSION OF SMARCB1 GROUP

1. Synovial sarcoma– Synovial sarcoma is classified as a tumor of uncertain differentiation, and some synovial sarcomas have rhabdoid cells.

SOME TUMOR SYNDROMES ASSOCIATED WITH SMARCB1

  1. Rhabdoid Tumor predisposition syndrome and
  2. Coffin -sirs syndrome.

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Reference: Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Kenichi kohashi and Yoshinao oda.