Molecular Genetics of Tumours Flashcards
Molecular Biomarkers in Lung Cancer
EGFR ALK ROS1 KRAS BRAF V600E MET
Genes involved in GIST
CKIT (exons 9 & 11, imatinib Rx)
PDGFRa
SDH A, B, C, D (young, do well)
NF1
Molecular Alterations in Spitz Naevi
NTRK 1,2,3 ALK ROS1 RET MET
Malignant Spitz - TERT promoter, p53
MDM2 Amplified Tumours
ALT / WDLPS / DDLPS
Low grade central osteosarcoma
Parosteal osteosarcoma
Intimal sarcoma
Molecular Changes in Adipocytic Tumours
MDM2 amplification: ALT / WDLPS / DDLPS
RB1 deletion in spindle cell lipoma
DDIT3 -FUS myxoid LPS
PLAG1 lipoblastoma
SMARCB1 (INI1) Deficient Tumours
Malignant rhabdoid tumour of kidney and soft tissue
CNS AT / RT
Epithelioid sarcoma (conventional and proximal)
Medullary renal carcinoma
SMARCB1-deficient sinonasal carcinoma
Poorly differentiated chordoma
SMARCA4 (BRG1) Deficient Tumours
SMARCA4 deficient thoracic carcinosarcoma
Small cell carcinoma of the ovary, hypercalcaemic type
SMARCA4 deficient undifferentiated uterine sarcoma
BCOR Rearranged Tumours
Kidney - Clear cell sarcoma (young children)
Uterus - HG ESS
Bone / Soft tissue - BCOR rearranged sarcoma
CNS - High grade neuroepithelial tumours with BCOR alteration
Molecular Changes in Bone Tumours
Osteochondroma: EXT1, EXT2 loss of function mutations
Enchondroma: IDH1, IDH2 mutations
Osteoid osteoma & OB: FOS, FOSB rearrangements
NOF: KRAS, FGFR1, NF1 alterations
Desmoplastic fibroma: CTNNB1, APC mutations
GCT of bone: H3 G34M mutation, RANKL overexp.
Chondroblastoma: H3 K36M mutation
ABC: USP6 rearrangement
LCH: BRAF V600E
Fibrous dysplasia: GNAS activating mutations
LG central & Parosteal OS: MDM2 amp, CDK4 (chr 12)
LG central CS: IDH1 / 2
LG peripheral CS: EXT1 / EXT2
Ewing Sarcoma: EWSR1 rearrangements
PMT: FGF gene rearrangements
Mesenchymal CS: HEY1-NCOA2 fusion
Molecular Changes in Thyroid Tumours
PTC: BRAFV600E mutations RAS mutations in encapsulated follicular variant RET, ALK and NTRK 1,3 fusions TERT promoter mutations
Follicular carcinoma:
RAS mutations
TERT promoter mutations
PAX8-PPAR fusion
Medullary:
RET activating mutations
Anaplastic carcinoma:
Same as above plus TP53, PTEN and Beta cat
Molecular Changes in Colorectal Carcinoma
BRAF V600E mutation
KRAS / NRAS / HRAS mutations
APC inactivation
Molecular Changes in Neuroblastoma
Poor prognosis:
MYCN amplification
1p, 11 q deletion, 17q gain
Diploidy
Better prognosis:
Hyperploidy
ETV6 Rearranged Tumours
Secretory carcinoma (breast, skin, salivary gland)
Congenital mesoblastic nephroma
Infantile fibrosarcoma
BRAF Altered Tumours
Mutations:
PTC, CRC, Melanoma, Histiocytic lesions, NSCLC, Metanephric adenoma, papillary craniopharyngioma
Fusions:
Spitzoid melanoma, Pilocytic astrocytoma
ALK Rearranged Tumours
ALK + ALCL ALK + DLBCL IMT Lung adenocarcinomas Neuroblastomas (some, point mutations)
EWSR1 Rearranged Tumours
Ewing sarcoma (FLI1, ERG, etc)
ESMC (NR4A3)
Desmoplastic small round cell tumour (WT1)
Myoepithelial tumour of soft tissue (ANF44, POU5F1)
Myxoid liposarcoma (DDIT3 / CHOP)
Clear cell sarcoma of soft tissue (ATF1)
Clear cell carcinoma of salivary gland (ATF1)
Angiomatoid fibrous histiocytoma (ATF1, CREB1)
Primary pulmonary myxoid sarcoma (CREB1)
Sclerosing epithelioid fibrosarcoma (CREB3L1)
FUS Rearranged Tumours
Angiomatoid fibrous histiocytoma (EWSR1)
LGFMS (CREB3L1/2)
Sclerosing epithelioid fibrosarcoma (CREB3L2)
Myxoid liposarcoma (DDIT3 / CHOP)
USP6 Rearranged Tumours
Primary ABC Giant cell lesion of the small bones Nodular fasciitis Myositis ossificans Fibroosseous pseudotumour of digits Cellular fibroma of tendon sheath
Molecular Alterations in Salivary Gland Tumours
Adenoid cystic carcinoma (MYB-NFIB, MYBL1-NFIB) Acinic cell carcinoma (NR4A3) Basal cell adenoma (CTNNB1) Clear cell carcinoma (EWSR1-ATF1) Epithelial - myoepithelial ca (HMGA2, PLAG1, HRAS) Low grade intraductal carcinoma (RET) Mucoepidermoid carcinoma (MAML2) Pleomorphic adenoma (HMGA2, PLAG1) Polymorphous adenocarcinoma (PRKD1) Secretory carcinoma (ETV6-NTRK3)
Molecular Alterations in Adult Kidney Tumours
Clear cell RCC - 3p deletion
Metanephric adenoma - BRAFV600E mutations
Molecularly Defined Tumours (WHO 2022) TFE3 rearranged RCC TFEB rearranged RCC ELOC mutated RCC FH deficient RCC SDH deficient RCC ALK rearranged RCC SMARCB1 deficient renal medullary carcinoma
Molecular Alterations in Paediatric Kidney Tumours
Wilms tumour - WT1 deletion / mutation (15%)
Cellular congenital mesoblastic nephroma (ETV6)
Malignant rhabdoid tumour of kidney (SMARCB1/ A4)
Clear cell sarcoma (BCOR ITD, YWHAE-NUTM)
Molecular Prognostic Markers in Gliomas
Better prognosis: IDH1 / 2 mutations MGMT methylation BRAFV600E mutations C-GIMP methylation 1 p / 19 q co -deletion (by virtue that oligos do better)
Worse prognosis:
TERT promoter mutations
EGFR amplication
Histone mutations
