Tumor Suppressor Genes – Mnemonics

Table of Contents

Today, we are going to talk only about the commonly mentioned tumor suppressor genes in the textbooks. This somewhat a “forced mnemonic” and may not be as effective and tedious to learn itself. If it works for you it’s well and good, if not find some other ways.

tumor suppressor cartoon
WassermanLab [CC BY-SA 4.0], via Wikimedia Commons

General Rules

1. Tumor suppressor genes of ‘p’ family are located in ‘p’ arm of chromosome e.g. p14, p16, p53, p73, etc. Remember PTEN and PTCH donot belong to ‘p’ family although they begin with letter ‘p’. But, PJS although not ‘p’ family is located in ‘p’ arm of chromosome.

2. Most tumor suppressor genes are located in ‘q’ arm of chromosome except VHL, WT1, MLH1/MSH2 and TSC-2, located in ‘p’ arm of chromosome.

Mnemonic: World Music TV

3. Most tumor suppressor genes are in odd-numbered chromosomes.

4. Tumors with ‘even numbers‘ in name are located in even-numbered chromosomes except BRCA2 and p16/p14.

Tumor Suppressor Genes on Odd-Numbered Chromosomes

1p: P73

  • Neuroblastoma

3p: VHL

Degrades hypoxia induced factors (HIFs), transcription factors that alters gene expression in response to hypoxia.

  • Von-Hippel Lindau syndrome:
    1. Cerebellar hemangioblastoma
    2. Clear cell renal carcinoma
    3. Pheochromocytoma
    4. Retinal angioma

3p: MLH1 (MutL homolog 1)

  • Hereditary nonpolyposis colon cancer type 2 (HNPCC2)

5q: APC

Negatively regulates the WNT pathway in colonic epithelium by promoting the formation of a complex that degrades beta-catenin.

  • Familial adenomatous polyposis/Colon cancer

7q: ST7 (Suppressor of Tumerogenicity protein 7)

  • Choriocarcinoma

9p: p16INK4 and p14ARF (CDKN2A)

Cyclin dependent kinase inhibitor that augments RB function and ARF which stabilizes p53.

  • Familial melanoma

9q: PATCHED (PTCH protein)

Encodes protein that is negative regulator of the Hedgehog signalling pathway.

  • Gorlin syndrome (Nevoid basal cell carcinoma syndrome)
  • Medulloblastoma

9q: TSC1 (Hamartin)

  • Tuberous sclerosis 1:EpiLoiA
    1. Epilepsy
    2. Low IQ
    3. facial Angiofibroma

11p: WT-1

  • Wilm’s tumor

11q: Menin (MEN 1 gene)

  • Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome:
    1. Pituitary adenoma
    2. Parathyroid adenoma
    3. Pancreatic islet cell tumor

In contrast, MEN 2 syndrome is associated with mutation in RET proto-oncogene.

13q: RB1

  • Familial retinoblastoma
  • Osteosarcoma

13q: BRCA2

  • Familial breast cancer (usually hormone receptor positive)
  • Ovarian cancer (lesser risk than BRCA1)
  • Higher risk of male breast cancer

15q: PML

  • Acute Promyelocytic Leukemia, i.e. M3 AML associated with t(15;17)

17p: p53

  • Li-Fraumeni syndrome:
    1. Brain tumors
    2. Sarcomas
    3. Leukemia
    4. Breast cancer

17q: BRCA1

  • Hereditary breast cancer (propensity for triple negativity) – higher risk than BRCA2
  • Ovarian cancer (higher risk than BRCA2)

17q: NF-1 (Neurofibromin)

GTPase that acts as negative regulator of RAS.

  • Neurofibromatosis type 1
    1. Multiple or plexiform neurofibromas
    2. Cafe-au-lait macules
    3. Freckling
    4. Optic glioma
    5. Lisch nodules (Iris hamartomas)
    6. Osseous lesion (Sphenoid dysplasia, thinning of long bone, pseudoarthrosis)

19p: PJS (LKB1 or STK11)

  • Peutz-Jegher’s syndrome
    1. Labial and oral mucosal hyperpigmentation
    2. Jejunal polyps (hamartomatous and adenomatous)
    3. Increased risk of cancer: Gastrointestinal (colorectal, gastric, pancreatic), breast, uterine, lung, ovary and sex-cords.

19q: Glioma Tumor Suppressor gene

  • Diffuse malignant glioma

Tumor Suppressor Genes on Even-Numbered Chromosomes

PTEN (Phosphatase and Tensin homolog): 10q

Negative regulator of PI3K/AKT signaling.

  • Cowden syndrome:
    1. Follicular thyroid cancer
    2. Breast cancer
    3. Endometrial cancer
    4. Multiple skin and mucosal hamartomas
    5. Macrocephaly and mental retardation

NF-2 (Neurofibromin-2 or Merlin): 22q

Cytoskeletal protein involved in contact inhibition.

  • Neurofibromatosis type 2:
    1. Bilateral vestibular schwannomas
    2. Multiple meningioma
    3. Glioma, neurofibroma, schwannoma
    4. Cataract (No lisch nodule)

TSC-2 (Tuberous sclerosis-2 or Tuberculin): 16p

  • Tuberous sclerosis 2:
    1. Benign hamartomas in many tissues
    2. Astrocytoma
    3. Rhabdomyosarcoma

E-cadherin (CDH1 or CD324): 16q

Important role in contact mediated growth inhibition of epithelial cells.

Also binds and sequesters beta-catenin of WNT signaling pathway.

  • Lobular breast cancer
  • Hereditary diffuse gastric carcinoma

MSH-2 (MutS homolog-2): 2p

  • Hereditary nonpolyposis colon cancer type 1 (HNPCC1)

SMAD2, SMAD4 (DPC) and DCC: 18q

  • DCC (Deleted in Colon cancer): Colorectal carcinoma
  • DPC (SMAD4): Pancreatic cancer, Colon cacner, Familial Juvenile Polyposis

Mnemonics to remember individual tumor suppressor genes

Neuroblastoma = Most common tumor within ONE year (Infatns) and most commonly metastasize to bONE: 1q

VHL and MLH1 = 3 letters (V, H and L or M, L and H) and exception to ‘q’ arm (WMTV): 3p

APC = Remember 5 lettered word “COLON” or “POLYP“: 5q

ST7 (Choriocarcinoma) = Name itself has ‘7’; also remember 7 lettered word “CHORION“: 7q

Melanoma = Remember 9 lettered word “EPIDERMIS” where melanocytes are located and since TSG belongs to p-family: 9p

Basal cell carcinoma = Remember 9 lettered word “BASAL CELL“: 9q (PTCH)

WT-1 = It has number “1” and letter “W” has 2 legs like number “11”; remember exception to ‘q’ arm (WMTV): 11p

MEN-1 = It has number “1” and letter “M” has 2 legs like number “11”: 11q

RB1 = Remember 13 lettered word “RETINAL CANCER”: 13q

APL (Acute promyelocytic leukemia) = Remember 15 lettered word “VITAMIN RECEPTOR”: 15q

p53 (Li-fraumeni syndrome) = Reverse “LI” of Li-fraumeni – it looks like “17”; remember p53 is a p-family: 17p

NF-1 and NF-2

  • Letter “NEUROFIBROMATOSIS” has 17 letters.
  • NF-1 has number “1”, hence give this to NF-1: 17q
  • NF-2 has number “2”, NF-2 has propensity of bilaterality of tumors be it schwannoma or meningioma; so bilateral number “2”: 22q

BRCA1 and BRCA2 = Just remember that in chronological order of chromosome number, BRCA2 comes before BRCA1. Both of these share their chromosome (although not the same locus) with other tumors:

  • BRCA1 (shares chromosome with NF-1): 17q
  • BRCA2 (shares chromsome with RB1): 13q

PJS = Just remember the 19 lettered word “PEUTZ JEGHER SYNDROME“; remember exception to “p” family: 19p

PTEN = As the name has “TEN”; remember it doesn’t belong to “p” family: 10q

MSH2 = As the name has number “2”; remember exception to “q” arm (WMTV): 2p

MLH1 has number “1” but is involved in HNPCC2.

MSH2 has number “2” but is involved in HNPCC1.

TSC-2 = Remember 16 lettered word “BENIGN HAMARTOMAS“; remember exception to “q” arm (WMTV) = 16p

E-Cadherin = Remember 16 lettered word “ADHERENS JUNCTION” or “CELL CELL ADHESION” = 16q

DCC and DPC = Remember 18 lettered word “COLORECTAL NEOPLASM” = 18q

Review:

GeneAssociated TumorChromosome
p73Neuroblastoma1
MSH2HNPCC 12
VHLRenal cell carcinoma3
MSH1HNPCC 23
APCColorectal cancer (associated with FAP)5
ST7Choriocarcinoma7
p16Melanoma9
PTCHBasal cell carcinoma (Gorlin syndrome)9
TSC1Tuberous sclerosis9
PTENCowden syndrome, Breast cancer, Endometrial cancer10
WT1Wilms’ tumor11
MeninMEN 1 syndrome11
RbRetinoblastoma and osteosarcoma 13
BRCA2Breast cancer13
PMLM3 ML15
TSC2Tuberous sclerosis16
E-cadherinGastric cancer16
NF1Neurofibromatosis type 117
BRCA1Breast and ovarian cancer 17
p53Most human cancers and Li-Fraumeni syndrome17
DPCPancreatic cancer (stands for deleted in pancreatic cancer)18
DCCColon cancer (stands for deleted in colon cancer)18
NF2Neurofibromatosis type 222


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