Genetic Basics and Cancer: Inheritance, Mutations, and Treatments

Gene

Fundamental unit of DNA; changes can be linked to diseases

Epigenetic changes

Alterations in gene expression due to environmental stressors, behavior, or lifestyle (exposure to chemicals, smoking etc.)

Pharmacogenetics

Gene function in health, disease and responses to medications

Genetic

Study of inherited traits

Genomics

Study of the interaction of all genetic material (not only genes)

DNA

Regulates and repairs function of the body

Double helix structure

Structure of nucleotides made of pentose sugar, phosphate, purine or pyrimidine nitrogen base

Nitrogen bases

DNA contains pairs of adenine, thymine, guanine and cytosine; in RNA, uracil replaces thymine

Genes

Nucleotide sequence that makes the basic unit of heredity

Exons

Portions of genome that encodes proteins

Introns

Portion of genome that does not code for protein

Codon

Start and stop sequences that signal a specific amino acid notifying enzymes to begin or halt production of a protein

Mutation

Damage or change to a gene that alters genetic code; may be inherited or occur sporadically

Germ cell mutations

Will affect gametes and pass the mutation to offspring

Somatic cell mutation

Will not be passed to offspring (such as that of sunburns on the skin)

Nomenclature

Naming and location of the chromosome; some genes have specific names (ex: BRCA1) and locus assigned based on where they fall on the chromosome number, arm and region

Short arm

p

Long arm

q

Centromere

The junction between the p and q portions of the arms

Human karyotype

Consists of 23 pairs of chromosomes, with 1-22 being autosomes and 23 being sex chromosomes

XX

Female

XY

Male

Y chromosome

Much smaller than the X chromosome

Chromosomal abnormalities

Downs syndrome: trisomy (3 copies) of chromosome 21; only trisomy compatible with life

Transcription

RNA polymerase uses DNA as a template to form an mRNA strand that will leave the nucleus to produce a protein

Spliceosomes

Excise introns

Translation

Ribosome reads mRNA transcript via tRNA

tRNA

One end binds to 3-nucleotide sequence of the mRNA and the other end corresponds with a specific amino acid that is linked to the protein chain.

Peptide bonds

Amino acids are linked together via peptide bonds.

Gene expression

All cells contain the same genes, but expression varies between cells.

Gene enhancers and silencers

Transcription factor binding sites on DNA that affect DNA transcription rates.

Allele

Gene inherited from one parent.

Genotype

Genetic information based on the genetic code.

Phenotype

Physical expression of genes - structure or appearance.

Recessive trait

Expressed only in a homozygous pairing of two identical alleles.

Dominant trait

Requires only one allele to be expressed.

Carrier

Person heterozygous for a recessive trait; will not manifest the trait but can pass it on to offspring.

Mendelian Inheritance

Copy of a gene inherited from each parent to make a punnett square.

Autosomal dominant

Single mutant allele from an affected parent is transmitted to an offspring regardless of sex.

Autosomal recessive

Manifested only when both members of the gene pair are affected.

X-linked recessive

Always associated with X chromosome; inheritance pattern is predominantly recessive.

Penetrance

Ratio of people with phenotype compared to genotype.

Expressivity

Relative severity of the genetic disorder, can vary for a given condition or from person to person.

Complex inheritance

Combination of one or more genes plus environmental triggers.

Single-Nucleotide Polymorphisms (SNPs)

Changes in one nucleotide of a gene sequence.

Mitochondrial DNA

Inherited from the mother; can be damaged from exposure to free radicals.

Pharmacogenomics

Interactions between a person's genetics and medications.

Oncogenes

Normal genes that control cell proliferation; mutation leads to activate oncogene.

Tumor suppressor genes

Inhibits uncontrolled cell proliferation.

Knudson's 'two hit' hypothesis

Both alleles must be damaged for cancer to develop.

Aneuploidy

Different number of chromosomes than 46.

Translocation

One piece of a chromosome breaking off and joining another.

Deletion

Piece of chromosome is broken off and lost.

Epigenetics

Not changing DNA, changing how it is read.

Genetic Assessment

Includes pedigree, karyotyping, and various screening methods.

Gene Therapy

Ex vivo: genetically defected cells modified then readministered back into the patient.

Cystic Fibrosis

Autosomal recessive defect in transmembrane conductance regulatory gene.

Downs Syndrome

Most common chromosomal disorder (trisomy 21) with a wide variety of severity.

Neoplasm

Abnormal growth, appearance and function of cells.

Immunocompetence

Immune system should destroy abnormal cells.

Tumor angiogenesis

Cancer cells need a blood supply so they secrete vascular endothelial growth factor.

Neoplasia

New growth; tumor

Benign

Abnormal cells that remain localized

Malignant

Replicating cancer cells that spread to other areas

Adenoma

Benign tumor of glandular tissue or organ

Lipomas

Collection of fat cells

Hemangioma

Collection of blood vessels on skin or internal organs

Desmoid tumor

Highly invasive but do not metastasize

Nevi

Moles; noncancerous

Myoma

Collection of muscle cells

Carcinoma

Malignant epithelial cells lining inner and outer surfaces

Adenocarcinoma

Cancer of glandular or ductal tissue

Sarcoma

Mesenchymal origin, such as connective tissue, cartilage, and bone

Osteoma

Benign tumor of bone

Chondroma

Benign tumor of the cartilage

Chondrosarcoma

Malignant tumor of cartilage

Leukemia

Cancerous changes in leukocytes

Lymphoma

Cancerous lymphocytes

TNM staging system

Tumor size 1-4, Node involvement 0-3, Metastasis to distant organs 0-1

Differentiation

Extent to which neoplastic cells resemble normal cells

Anaplasia

Lack of differentiation - not good

Stem cells

New cells that are not specified

Paraneoplastic syndrome

Unexpected pathology provoked by presence of cancer

Cancer cachexia

Progressive loss of body fat and lean body mass

Direct invasion

Causing tissue death, hemorrhage, and blocking important functions

Surgery

Highest cancer cure rate with solid, well circumscribed tumors

Radiation

Kills everything it's exposed to by frying DNA and stopping replication

Chemotherapy

Cytotoxic drugs destroy cells (actively kill)

Immunotherapy

Wakes up the immune system by enhancing its response to cancer cells

Autonomy

Cancerous cells grow without restrictions that regulate cell growth

Metastasis

Cancer cells travel from the place of origin to develop new tumors in other areas of the body

Angiogenesis

Abnormal cells release enzymes to generate blood vessels and supply oxygen and nutrients contributing to growth

Cell cycle drugs

True chemotherapy drugs are limited to four broad categories

Adjuvant therapy

Working alongside other treatment methods (surgery, radiation, and chemo)

Neoadjuvant therapy

Used before other treatment to shrink tumors

Palliative chemotherapy

When cure is not feasible but treatment could slow progression or manage symptoms

Antineoplastic agents

Chemotherapy agents including alkylating agents, antimetabolites, and others

Cyclophosphamide

Administered orally and IV; more effective IV

Methotrexate

Affects cells with high metabolic rates

Doxorubicin

Interferes with DNA replication and RNA transcription of cancer cells