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| Translocation | Fusion / Effect | Cancer | Drug / Note |
|---|---|---|---|
| t(9;22) | BCR-ABL p210 — constitutive TK | CML; also Ph+ ALL (p190) | Imatinib, dasatinib, ponatinib (T315I) |
| t(15;17) | PML-RARα — blocks myeloid differentiation | AML-M3 (APL); DIC | ATRA + arsenic trioxide |
| t(8;21) | AML1-ETO (RUNX1-RUNX1T1) | AML-M2 | Good prognosis; high-dose AraC |
| inv(16)/t(16;16) | CBFβ-MYH11 | AML-M4Eo; abnormal eos | Good prognosis |
| t(8;14) | c-MYC to IgH; MYC overexpression | Burkitt lymphoma | Starry sky; Ki-67 ~100% |
| t(2;8), t(8;22) | c-MYC to Igκ or Igλ | Burkitt variants | Same biology as t(8;14) |
| t(14;18) | BCL-2 to IgH; blocks apoptosis | Follicular lymphoma | Most common adult NHL; indolent |
| t(11;14) | Cyclin D1 overexpression | Mantle cell lymphoma | CD5+, CD23−; poor prognosis |
| t(2;5) | NPM-ALK — constitutive ALK kinase | ALCL (T-cell) | CD30+; crizotinib |
| t(11;22)(q24;q12) | EWSR1-FLI1 — aberrant TF | Ewing sarcoma | Diaphysis; onion-skin; small blue cells |
| t(X;18) | SS18-SSX1/2 — aberrant repressor | Synovial sarcoma | Biphasic; near joints; TLE1+ |
| t(12;21) | TEL-AML1 (ETV6-RUNX1) | Pediatric B-ALL | Best prognosis ALL; cryptic |
| t(4;11) | MLL-AF4 | Infant ALL (<1yr) | Worst pediatric ALL prognosis |
| t(1;19) | E2A-PBX1 | Pre-B ALL | Intermediate prognosis |
| t(9;22) in ALL | BCR-ABL p190 | Ph+ ALL (adult) | Poor; TKI + chemo |
| t(3;8) / RET/PTC | RET/PTC rearrangements | Papillary thyroid carcinoma | Also BRAF V600E (point mut) |
| t(2;3)(q13;p25) | PAX8-PPARγ | Follicular thyroid carcinoma | FNA cannot diagnose FTC alone |
| inv(3)/t(3;3) | GATA2 enhancer → EVI1 overexpression | AML; adverse risk | Thrombocytosis; dysplastic megas |
| t(6;9) | DEK-NUP214 | AML; adverse risk | Basophilia; FLT3-ITD co-mutation >70% |
| t(5;12) | TEL-PDGFRB (ETV6-PDGFRB) | CEL / MPN with eosinophilia | Exquisitely imatinib-sensitive |
| t(11;22) EWSR1-WT1 | Polyphenotypic fusion TF | DSRCT | Young males; abdominal; poor prognosis |
| Alkylator-related secondary AML | -5/del(5q), -7/del(7q) | t-MDS/AML | Latency 4-8yr; poor prognosis |
| Topo II-related secondary AML | MLL (11q23) or RUNX1 (21q22) balanced translocations | t-AML | Latency 1-3yr; anthracyclines, etoposide |
| Marker | Cancer(s) | Important False Positives | Key Notes |
|---|---|---|---|
| AFP | HCC, yolk sac tumor, hepatoblastoma | Pregnancy, acute hepatitis flare, cirrhosis | ANY AFP in GCT = non-seminomatous element; >400 = HCC diagnosis in cirrhosis+LI-RADS5 |
| β-hCG | Choriocarcinoma, hydatidiform mole, mixed GCT | Pregnancy, marijuana | Seminoma: AFP must = 0; any AFP = non-seminomatous |
| CEA | Colorectal, gastric, pancreatic, lung, breast | Smoking (most important), IBD, cirrhosis, pancreatitis | Main use: monitor CRC recurrence post-resection; not for diagnosis |
| CA-125 | Serous ovarian, endometrial | Endometriosis, menstruation, pregnancy, cirrhosis, PID | Not a screening test; monitor recurrence |
| CA 19-9 | Pancreatic, cholangiocarcinoma, gastric | Biliary obstruction (critical!), pancreatitis, PSC | Unreliable when jaundiced; Lewis antigen-negative → false negative |
| CA 15-3 / CA 27.29 | Breast cancer | Benign breast disease, liver disease | Marker flare: transient rise with effective therapy — do not change treatment |
| PSA | Prostate cancer | BPH, prostatitis, recent ejaculation/DRE | BCR post-prostatectomy: PSA ≥0.2 ng/mL × 2; PSADT <3mo = systemic disease |
| Calcitonin | Medullary thyroid carcinoma | Hypercalcemia (other causes) | Screen MEN2A/2B families; prophylactic thyroidectomy |
| Thyroglobulin | Papillary, follicular thyroid carcinoma | Benign thyroid disease | Should be undetectable after total thyroidectomy + RAI; any rise = recurrence |
| 5-HIAA (urine) | Carcinoid tumor | Serotonin-rich foods, SSRIs | Carcinoid syndrome only with liver mets (bypasses first-pass metabolism) |
| LDH | Lymphoma, testicular GCT (staging) | Hemolysis, MI, liver disease, PE | Non-specific but prognostic in lymphoma; elevated in dysgerminoma |
| Inhibin A/B | Granulosa cell tumor (ovarian) | — | FOXL2 mutation; Call-Exner bodies; estrogen → endometrial hyperplasia |
| CD15+, CD30+ | Reed-Sternberg cells (Hodgkin lymphoma) | — | EXCEPTION: LPHL = CD20+, CD15−, CD30− |
| CLL phenotype | CLL: CD5+, CD19+, CD20(dim)+, CD23+ | — | vs Mantle cell: CD5+, CD19+, CD23−, Cyclin D1+ |
| HCL phenotype | HCL: CD11c+, CD25+, CD103+, TRAP+ | — | BRAF V600E; cladribine; dry tap on biopsy |
| Syndrome | Cancer | Mediator / Antibody | Key Distinguishing Feature |
|---|---|---|---|
| SIADH | SCLC | Ectopic ADH | Hyponatremia, euvolemic; urine Na >20, concentrated urine |
| Ectopic ACTH (Cushing) | SCLC, carcinoid, MTC, thymoma | Ectopic ACTH → bilateral adrenal hyperplasia | ↓K+, HTN, hyperglycemia; no dex suppression |
| Lambert-Eaton (LEMS) | SCLC | Anti-P/Q-type VGCC | Weakness IMPROVES with repetition; ↓DTRs. Opposite of MG |
| Myasthenia gravis | Thymoma | Anti-AChR | Weakness WORSENS with repetition; ptosis, diplopia |
| Hypercalcemia of malignancy | SCC lung, RCC, breast, MM | PTHrP (most common) | ↑Ca, ↓PO4, ↓PTH (distinguishes from hyperPTH) |
| Cerebellar degeneration | SCLC, breast, ovarian | Anti-Yo (anti-Purkinje), Anti-Hu | Truncal ataxia, dysarthria, nystagmus |
| Limbic encephalitis | SCLC, testicular teratoma | Anti-Hu, anti-NMDAR | Memory loss, seizures, psychiatric sx |
| Trousseau syndrome | Pancreatic, GI, lung | Tumor mucin activates clotting | Migratory superficial thrombophlebitis |
| Dermatomyositis | Ovarian, lung, GI, breast | Autoimmune; anti-Mi-2 | Heliotrope rash, Gottron papules, ↑CK |
| Carcinoid syndrome | Carcinoid with LIVER METS | Serotonin, bradykinin | DAFE: Diarrhea, wheezing, Flushing, right-sided Endocardial disease |
| Erythrocytosis | RCC, HCC, hemangioblastoma | Ectopic EPO (HIGH EPO) | vs PV: LOW EPO + JAK2 V617F in PV |
| Nephrotic syndrome (MCD) | Hodgkin lymphoma | Lymphokine damage to GBM | Foot process effacement; no immune deposits |
| Gene | Type | Cancer | Drug / Notes |
|---|---|---|---|
| KRAS | GTPase (signal) | Pancreatic (90%), CRC, lung | KRAS G12C → sotorasib/adagrasib; mutant = anti-EGFR resistant |
| HER2/ERBB2 | RTK — amplified | Breast (25%), gastric, ovarian | Trastuzumab; T-DXd; monitor for cardiomyopathy |
| EGFR | RTK — mutated | NSCLC adenocarcinoma | Exon 19 del / L858R → osimertinib; T790M = resistance |
| ALK fusions | RTK — fusion | NSCLC (3%), ALCL | EML4-ALK in lung; crizotinib/alectinib |
| RET | RTK — mutation/fusion | MTC (MEN2), papillary thyroid, NSCLC | Selpercatinib/pralsetinib; prophylactic thyroidectomy in MEN2 |
| BCL-2 | Anti-apoptotic | Follicular lymphoma (t(14;18)), CLL | Venetoclax targets BCL-2 |
| BRAF V600E | Ser/Thr kinase | Melanoma (50%), papillary thyroid, HCL, CRC (right-sided) | Dabrafenib + trametinib; BRAF mut CRC = poor prognosis; rules out Lynch |
| JAK2 V617F | Non-receptor TK | PV (>95%), ET, PMF | Ruxolitinib; JAK-STAT pathway |
| c-MYC / N-MYC | Transcription factor | Burkitt (c-MYC); Neuroblastoma (N-MYC amplification) | N-MYC ≥10 copies = poor prognosis neuroblastoma |
| KIT (CD117) | RTK — mutated | GIST, AML-M3, mastocytosis | Imatinib for GIST; PDGFRA D842V = imatinib resistant → avapritinib |
| Gene (Chr) | Cancer / Syndrome | Function |
|---|---|---|
| TP53 (17p13) | Most cancers; Li-Fraumeni syndrome | p21 activation → G1 arrest; BAX → apoptosis; MDM2 degrades p53 |
| RB1 (13q14) | Retinoblastoma, osteosarcoma, SCLC | Binds E2F; CDK4/6 + CycD phosphorylates RB → releases E2F → S phase |
| BRCA1 (17q21) | Breast (70%), ovarian, prostate | Homologous recombination repair; PARP inhibitor synthetic lethality |
| BRCA2 (13q12) | Breast, ovarian, pancreatic, MALE breast | HR repair; BRCA2 unique: male breast ca, pancreatic ca |
| APC (5q21) | FAP → CRC; desmoids | Degrades β-catenin (Wnt OFF); loss → nuclear β-catenin → MYC, Cyclin D1 |
| MLH1/MSH2/MSH6/PMS2 | Lynch syndrome (HNPCC) → CRC, endometrial | Mismatch repair; MSI-H; BRAF WT in Lynch (BRAF mut = sporadic) |
| VHL (3p25) | Clear cell RCC, hemangioblastoma, pheochromocytoma | Degrades HIF-1α; VHL loss → ↑VEGF + EPO |
| PTEN (10q23) | Endometrial, prostate, breast; Cowden syndrome | Opposes PI3K/AKT; loss → ↑AKT survival signaling |
| NF1 (chr 17) / NF2 (chr 22) | NF1: neurofibromas, MPNST; NF2: bilateral acoustic neuromas | NF1 = RAS-GAP (inactivates RAS); NF2 = merlin (cytoskeleton) |
| WT1 (11p13) | Wilms tumor; WAGR, Denys-Drash | Renal/gonadal TF; two-hit model |
| Drug | Mechanism | Unique Toxicity | Antidote / Prevention |
|---|---|---|---|
| Methotrexate | DHFR inhibitor → ↓THF (S-phase) | Mucositis, myelosuppression, nephrotoxicity (high dose) | Leucovorin (folinic acid) |
| 5-FU | Thymidylate synthase inhibitor (S-phase) | Hand-foot syndrome, mucositis; DPD deficiency → fatal toxicity | Leucovorin enhances efficacy |
| Cyclophosphamide | Alkylating agent (non-cycle specific) | Hemorrhagic cystitis (acrolein metabolite) | MESNA + IV hydration |
| Busulfan | Alkylating agent | Pulmonary fibrosis, hyperpigmentation, seizures | Phenytoin (seizure prophylaxis) |
| Cisplatin | Platinum cross-links (non-cycle) | Nephrotoxicity, ototoxicity, neuropathy | IV hydration, amifostine |
| Carboplatin | Platinum (non-cycle) | Primarily myelosuppression; less nephro/oto than cisplatin | Dose by AUC (Calvert formula) |
| Oxaliplatin | Platinum (non-cycle) | Cumulative sensory neuropathy (cold-triggered initially) | Used in CRC (FOLFOX, CAPOX) |
| Bleomycin | Free radical DNA breaks (G2) | Pulmonary fibrosis; worsened by high FiO2 | Low FiO2; monitor PFTs |
| Doxorubicin | Topo II inhibitor + free radicals | Dilated cardiomyopathy (cumulative, irreversible) | Dexrazoxane; lifetime limit ~550 mg/m² |
| Vincristine | Tubulin polymerization block (M-phase) | Peripheral neuropathy + constipation; minimal marrow | "Vincristine = nerves" |
| Vinblastine | Tubulin polymerization block (M-phase) | Myelosuppression (dose-limiting) | "Vinblastine = blood" |
| Paclitaxel | Microtubule stabilization (M-phase) | Myelosuppression, neuropathy; hypersensitivity (Cremophor) | Pre-medicate: dex + antihistamine |
| Irinotecan | Topoisomerase I inhibitor | Early (cholinergic) diarrhea + late (secretory) diarrhea | Early → Atropine; Late → Loperamide |
| Etoposide | Topoisomerase II inhibitor | Myelosuppression; secondary AML (MLL translocation) | Latency 1-3 years |
| ATRA | Differentiates APL cells via PML-RARα | Differentiation syndrome: fever, pulm infiltrates, renal failure | Dexamethasone; do NOT stop ATRA |
| Tamoxifen | SERM (ER antagonist in breast) | Endometrial cancer; DVT/PE; hot flashes | AIs preferred postmenopause (no uterine risk) |
| 6-Mercaptopurine | Purine synthesis inhibitor (S-phase) | Myelosuppression, hepatotoxicity | Reduce dose 75% if on allopurinol (blocks XO → ↑6-MP) |
| Asparaginase | Depletes asparagine (G1-specific) | Pancreatitis, coagulopathy (↓fibrinogen, ↓AT-III) | Pediatric ALL (PEGylated = pegaspargase) |
| Syndrome | Components | Gene | Key Rule |
|---|---|---|---|
| MEN1 | Parathyroid (90%) + Pituitary (prolactinoma) + Pancreas (gastrinoma) | MEN1 (menin), 11q13 | "3 Ps": Parathyroid, Pituitary, Pancreas |
| MEN2A | MTC (100%) + Pheo (50%) + Parathyroid (20%) | RET, codon 634 | Rule out pheo BEFORE thyroid surgery |
| MEN2B | MTC (most aggressive) + Pheo + Mucosal neuromas + Marfanoid habitus | RET M918T (de novo) | NO parathyroid; most aggressive MTC |
| Syndrome | Gene / Chr | Cancers | Distinguishing Feature |
|---|---|---|---|
| FAP | APC, 5q21 | CRC (100% by 40s) | >100 polyps; prophylactic colectomy; Gardner = desmoids + osteomas |
| Lynch (HNPCC) | MLH1/MSH2/MSH6/PMS2 | CRC (right-sided), endometrial, ovarian, urinary tract | MSI-H; BRAF WT rules OUT Lynch |
| Peutz-Jeghers | STK11/LKB1 | GI, breast, pancreatic, gynecologic | Perioral melanin spots; hamartomatous polyps |
| Li-Fraumeni | TP53 | Sarcomas, breast, brain, adrenal, leukemia | Germline TP53; early onset; SBLA mnemonic |
| VHL | VHL, 3p25 | Clear cell RCC, hemangioblastoma, pheo | VHL loss → ↑HIF-1α → ↑VEGF + EPO |
| Cowden | PTEN, 10q23 | Breast, follicular thyroid, endometrial | Hamartomas; macrocephaly; PTEN opposes PI3K |
| Gorlin | PTCH1 | Multiple BCCs, medulloblastoma (desmoplastic) | Jaw cysts, calcified falx; vismodegib for BCC |
| NF-1 | NF1, chr 17 | Neurofibromas, MPNST, optic glioma | ≥6 café-au-lait spots; Lisch nodules; axillary freckling; NF1 = RAS-GAP |
| NF-2 | NF2, chr 22 | Bilateral acoustic neuromas, meningiomas, ependymomas | "22 = 2 ears" |
| HDGC | CDH1 (E-cadherin) | Diffuse gastric cancer (70%), lobular breast ca | Prophylactic total gastrectomy; occult signet ring cells |
| Organ | Top Primary Sources | Key Feature |
|---|---|---|
| Bone | Breast, Lung, Thyroid, Kidney, Prostate | Blastic (prostate) vs Lytic (MM — no alk phos rise, RCC, thyroid); pathologic fractures |
| Brain | Lung (#1 overall), Breast, Melanoma, RCC, Colon | Gray-white junction; multiple lesions; melanoma = most hemorrhagic |
| Liver | CRC (#1 in US), pancreatic, gastric, breast, carcinoid | Carcinoid liver mets → carcinoid syndrome; multiple nodules |
| Lung (cannonball mets) | RCC, choriocarcinoma, sarcoma, CRC, breast | Round, well-defined; RCC and choriocarcinoma = hemorrhagic |
| Ovary (Krukenberg) | Gastric (most common), CRC, breast (lobular), appendiceal | Bilateral; signet ring cells; mucin-secreting |
| Spinal cord | Breast, lung, prostate (extradural, most common) | EMERGENCY: immediate dexamethasone + STAT MRI; radiation ± surgery |
| Left supraclavicular node | GI (gastric, pancreatic, colon), pelvic | Virchow's node (Troisier sign): thoracic duct drains abdominal viscera → left subclavian junction |
| Umbilical nodule | GI (gastric, pancreatic, colon), ovarian | Sister Mary Joseph nodule; falciform ligament spread; indicates Stage IV |
| Adrenal | Lung (#1), breast, melanoma, RCC | Bilateral adrenal masses → mets until proven otherwise; adrenal insufficiency if bilateral |
| Emergency | Presentation | Immediate Treatment |
|---|---|---|
| Spinal cord compression | Back pain + bilateral leg weakness + bowel/bladder dysfunction | High-dose dexamethasone IMMEDIATELY → STAT MRI → radiation ± surgery |
| SVC syndrome | Facial/arm edema, neck vein distension, facial cyanosis | HOB elevation, steroids, radiation (SCLC/NHL), stenting |
| Tumor lysis syndrome | ↑K, ↑PO4, ↑uric acid, ↓Ca after chemo (Burkitt, ALL) | IV hydration, allopurinol/rasburicase; monitor electrolytes |
| Febrile neutropenia | Temp ≥38.3°C + ANC <500 | Blood cultures → IV antibiotics (cefepime) within 60 minutes |
| Hypercalcemia of malignancy | Confusion, polyuria, constipation, Ca >12 | IV saline → zoledronic acid → calcitonin (bridge) → denosumab if refractory |
| Leukostasis | WBC >100k + confusion + pulmonary infiltrates | Leukapheresis + hydroxyurea; avoid RBC transfusion |