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Fitz 9th > 19 - Carcinogenesis and Skin > Flashcards

19 - Carcinogenesis and Skin Flashcards

1
Q

Combined incidence of SCC and BCC is likely to be at least _____fold higher than that of all other cancers combined

A

Two

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2
Q

Whereas single base mutations in early SCC lesions frequently are characteristic of _____-induced damage, later changes are associated with _____

A

UV light

Genomic instability

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3
Q

_____ mutations are characteristic of chemical mutagens used to initiate tumor formation

A

Ras

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4
Q

Most events occur early in the progression sequence in (UV-induced tumors/chemical carcinogenesis), but in (UV-induced tumors/chemical carcinogenesis), most events occur late and often do not bear the signatures of the original mutagen

A

UV-induced tumors

Chemical carcinogenesis

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5
Q

A driving force underlying neoplastic progression is ______, which enables the accumulation of mutations involving oncogenes and tumor suppressor genes that contribute to the observed abberations in tumor cell function

A

Defective DNA repair

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6
Q

Tumors contain a small number of self-renewing stem cells that produce transient-amplifying and differentiating progeny

A

Cancer stem cells or

Tumor-initiating cells

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7
Q

Constitute the overwhelming majority if cells in a tumor

A

Transient-amplifying and differentiating progeny

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8
Q

Y/N: Transformation of different cell populations produces different tumor subtypes, so a tumor’s cell of origin is a key determinant of its ultimate phenotype

A

Yes

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9
Q

Any gene that can transform normal cells in culture and induce cancer in animals

A

Oncogene

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10
Q

Most oncogenes are derived from

A

Proto-oncogenes

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11
Q

Negatively regulate cell proliferation, cause apoptosis, repair damaged DNA, or induce cellular differentation

A

Tumor suppressor genes

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12
Q

In contrast to (oncogenes/tumor suppressor genes), which typically require that only one allele undergo activation via mutation, both alleles of (oncogenes/tumor suppressor genes) must be inactivated to promote tumor development

A

Oncogenes

Tumor suppressor genes

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13
Q

Markedly increased risk of developing BCCs which arise at a younger age and appear in greater numbers
Predisposed to the development of a pediatric brain tumor arising in the cerebellum, medulloblastoma, as well as a variety of other defects throughout the body, including bifid ribs, calcified falx cerebri, odontogenic keratocysts, frontal bossing, palmar pits

A

Nevoid BCC syndrome

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14
Q

NBCCS is caused by germline mutations disrupting the

A

PTCH1 gene

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15
Q

Deregulated activity of the ______ pathway is detected in essentially all BCCs

A

Hedgehog

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16
Q

Inherited cancer syndromes that exclusively predispose to cutaneous SCC

A

None

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17
Q

Extreme photosensitivity and stark acceleration in the onset of skin cancer
Lack of nucleotide excision repair

A

Xeroderma pigmentosum

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18
Q

Subepidermal blistering, nonhealing wounds, high predisposition to SCC
Caused by loss-of-function mutations in COL7A1

A

Recessive dystrophic epidermolysis bullosa

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19
Q

Susceptibility to keratoacanthomas

Heterozygous germline inactivation of TGF-betaR1

A

Smith-Ferguson syndrome

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20
Q

_____ mutations occur at more than 70% frequency across all SCCs

A

TP53

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21
Q

_____ famiy genes are mutated in more than 70% of cutaneous SCC, 20% of oral head and neck SCC, 13% of lung SCC, and 10% of esophageal SCC

A

NOTCH

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22
Q

_____ amplication is a common lineage-specific driver of SCC

A

SOX2

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23
Q

Upregulation of _____ and _____ prheay signaling across the progression sequence of SCC development

A

ERK

mTOR (mammalian target of rapamycin)

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24
Q

BRAF inhibition used for

A

Melanoma

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25
Q

SMO inhibition used for

A

BCC

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26
Q

First FDA-approved BRAF inhibitor

A

Vemurafenib

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27
Q

More potent BRAF inhibitors less frequently observed adverse effects such as development of SCC and keratoacanthoma-like lesions

A

Dabrafenib

Encorafenib

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28
Q

The concomitant use of _____ with BRAF inhibitors almost completely suppress the emergence of SCCs

A

MEK

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29
Q

The long-term treatment of BCCs with the SMO inhibitor _____ has occasionally been associated with the evolution of treated tumors to a SCC morphology

A

Vismodegib

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30
Q

Primary etiologic agent for all skin cancers

Major carcinogen in the human environment

A

Ultraviolet radiation

31
Q

Most clear-cut etiologic factor in human malignancy

A

Ultraviolet radiation

32
Q

With PUVA therapy, the risk of SCC was more than _____-fold higher and the risk of BCC was more than _____-fold higher

A

100

11

33
Q

UVB and UVC tend to be absorbed at the

A

5-6 double bond of pyrimidines (thymine and cytosine)

34
Q

If two adjacent pyrimidines are activated, the resulting open bond cross-react, creating a

A

Cyclobutane pyrimidine dimer

35
Q

Most frequent CPD

A

TT

36
Q

A single bond between the 6 position of one pyrimidine and the exocyclic group of the other instead creates a

A

Pyrimidine (6-4) pyrimidone photoproduct

37
Q

Most frequent (6-4)PP

A

TC

38
Q

Although there is _____-fold more UVA than UVB in sunlight, UVA requires up to _____-fold greater doses fo some of its biological effects

A

20

1000

39
Q

Ratio of DNA photoproducts

A

6 CPDs per 1 (6-4)PP

40
Q

Accounts for only 5% of UVR but produces majority of UV-induced DNA lesions

A

UVB

41
Q

UV signature mutation

A

C > T

42
Q

UVA fingerprint changes

A

T > G

43
Q

UV-induced generation of the ROS _____ was found to interact with melanin, resulting in chemoexcitation of electrons in melanin to extremely high-energy states, analogous to reactions that culminante in bioluminescence

A

Peroxynitrite

44
Q

Instead of generating light, excited electrons in melanin can directly interact with DNA, resulting in continuous CPD formation for hours after UVA or UVB exposure has ceased, so-called

A

“Dark CPDs”

45
Q

Chronically UV-exposed clinically and histologically normal-appearing epidermis harbors about _____ mutations per megabase of DNA

A

5

46
Q

Have the highest mutational loads of any human cancer

A

Skin cancer

47
Q

Estimates of the rate of progression of AK to SCC range from _____% at 1 year to _____% in 4 years

A
  1. 6

2. 6

48
Q

Y/N: Molecular profiles of most AKs are largely indistinguishable from those of well-differentiated invasive SCC

A

Yes

49
Q

Virus-associated cancers comprise up to _____% of all human malignancies

A

10

50
Q

Y/N: Viral transformation is a dead end for viruses

A

Yes

51
Q

More than 200 types of HPVs have been identified and grouped into five genera, with the _____ HPV types most closely linked to cancer

A

Alpha

Beta

52
Q

Produce condylomata, cervical cancer, most anorectal cancers, and a sizeable fraction of genital and oropharyngeal cancers

A

Alpha HPVs

53
Q

Linked to the development of cutaneous warts and SCC in individuals with epidermodysplasia verruciformis

A

Beta HPVs

54
Q

Unlike the (alpha/beta) HPVs, there has been no evidence for viral transcripts in skin cancers, indicating that (alpha/beta) HPVs are not required for tumor maintenance

A

Alpha

Beta

55
Q

Y/N: Human polyomavirus infections are ubiquitous

A

Yes

56
Q

Associated with the development of posttransplant nephropathy

A

BKPyV

57
Q

Causes progressive multifocal leukoencephalopathy

A

JCPyV

58
Q

Associated with pruritic and dyskeratotic dermatoses

A

HPyV6

HPyV7

59
Q

Associated with trichodysplasia spinulosa

A

TSPyV

60
Q

Detected in about 80% of Merkel cell carcinomas

A

MCPyV

61
Q

First link between an occupational exposure and the development of cancer
First example of chemical carcinogenesis

A

Scrotal cancer in chimney sweeps

62
Q

The excess risk of skin cancer associated with ionizing radiation exposure is almost exclusively confined to

A

BCC

63
Q

Skin cancers that arise in sites of chronic ulcers or scars, most often caused by burns

A

Marjolin ulcers

64
Q

Marjolin ulcers most often occur on

A

Lower extremities

Scalp

65
Q

Almost 90% of Marjolin tumors are

A

SCC

66
Q

Y/N: Marjolin ulcer SCCs are less aggressive

A

No - highly aggressive

67
Q

Only benign papillomas developed in mice with Hras expression targeted to

A

Interfollicular epidermis

68
Q

Expression of Hras in _____ that included stem cells led to spontaneous SCC development

A

Hair follicle epithelia

69
Q

Two most frequently mutated genes in SCC

A

Notch1

Trp53

70
Q

Mutations in sporadic BCCs

A

PTCH1 or SMO

71
Q

Hair follicle stem cells are largely resistant to SCC development during

A

Telogen

72
Q

Low-level Hedgehog signaling produced _____ and high-level signaling yielded _____

A

Basaloid hamartomas

Nodular tumors

73
Q

Most frequently used rodent model for UV-induced skin cancers
Outbred strain that lacks a functional Hairless gene - undergo one round of anagen soon after birth, after which point follicles degenerate into cystic structures

A

Immunocompetent Hairless mouse

Fitz 9th (108 decks)

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