The Influence of Pigment Transfer on the Risk of Developing Melanoma: The Significance of the Melanocyte Amputation Cycle


  • Patrick A. Riley Totteridge Institute for Advanced Studies, The Grange, Grange Avenue, London N20 8AB UK



Epigenetic, progression, melanoma, cytocrine transfer, stem cell proliferation.


 It has been shown that cancer incidence is not only a function of the size of the population at risk but is strongly associated with the turnover rate of the tissue concerned. There is a strong negative correlation between melanoma incidence and the degree of skin pigmentation, and yet the melanocyte density is the same for all races. The proposal advanced in this communication is that the probability of undergoing malignant change is critically dependent on the melanocyte turnover and that this is regulated by the pigmentation process.

In melanocytes, the division rate is influenced by the process of pigment donation, probably by a mechanism whereby the continual cytoplasmic loss due to cytocrine transfer of melanosomes (termed the ‚Amputation Cycle‚) inhibits replication. Consequently the turnover of melanocyte stem cells in heavily pigmented epidermis will be diminished, and this is held to account for the strong negative correlation between the degree of skin pigmentation and melanoma incidence.


Armitage P, Doll R. The age distribution of cancer and a multistage theory of carcinogenesis. Brit J Cancer 1954; 8: 1-12.

Burnet FM. Cancer: Somatic genetic considerations. Adv Canc Res 1978; 28: 1-29.

Burch PJR. Natural and radiation carcinogenesis in man. Proc Roy Soc Lond 1965; B162: 223-287.

Penrose LS. Mutation. In: LS Penrose LS, Brown HL, editors. Recent advances in human genetics. London: J & A Churchill Ltd. 1961. p. 1-18.

Fraser GR. Our genetical load. Ann Hum Genet 1962; 25: 387-415.

Loeb LA, Springgate CF, Battula N. Errors in DNA replication as a basis of malignant changes. Cancer Res 1974; 34: 2311-2321.

Riley PA. Is the establishment of a clone exhibiting defective DNA repair the initial stage of carcinogenesis? Med Hypoth 1982; 9: 163-168.

Riley PA. Is the initial event in carcinogenesis an enhancement of the mutation rate? Free Rad Res Comms 1990; 11: 59-63.

Loeb LA. Transient expression of a mutator phenotype in cancer cells. Science 1997; 277: 1449-1450.

Riley PA. Biochemical features of malignant cell populations. In: Kotyk A, editor. Highlights of modern biochemistry. 1989. Vol. 2, p. 1445-1457.

Lynch M. Rate, molecular spectrum, and consequences of human mutation. Proc Natl Acad Sci USA 2010; 107: 961-968.

Holliday R. A new theory of carcinogenesis. Brit J Canc 1979; 40: 513-522.

Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 194: 23-28.

Nowell PC. Tumor progression and clonal evolution: The role of genetic instability. In: German J, editor. Chromosome mutation and neoplasia. New York: Alan R Liss Inc. 1983; p. 413-432.

Berenblum L. Carcinogenesis as a biological problem. New York: Elsevier Press. 1974.

Curtis HJ. Somatic mutations in radiation carcinogenesis. In: Radiation-induced Cancer. Vienna: Int. Atomic Energy Agency. 1969. p. 45-55.

Hirsch HR. The multistep theory of aging: relation to the forbidden clone theory. Mech. Aging & Develop 1975; 3: 165-172.

Riley PA. Failure of fidelity of vertical transmission of epigenetic patterning as the basis of cancer. Melanoma Res. 2014; 24: 424-427.

Riley PA. Cancer is the outcome of defective epigenetic copying of the pattern of selective gene activity in differentiated cells. Cancer Res Frontiers 2015; 1: 280-287.

Tomasetti C, Vogelstein B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2015; 347: 78-81.

Szabo G. The regional anatomy of the human integument with special reference to the distribution of hair follicles, sweat glands and melanocytes. Phil Trans R Soc Lond 1967; B252: 447–485.

Bataille V, Grulich A, Sasieni P, Swerdlow A, Newton Bishop J, McCarthy W, Hersey P, Cuzick J. The association between naevi and melanoma in populations with different levels of sun exposure: a joint case-control study of melanoma in the UK and Australia. Br J Cancer 1998; 77: 505-510.

Gandini S, Sera F, Cattaruzza MS, Pasquini P, Abeni D, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer 2005; 41: 28-44.

Chang YM, Newton-Bishop JA, Bishop DT, Armstrong BK, Bataille V, Bergman W, Berwick M, Bracci PM,Elwood JM, Ernstoff MS, Green AC, Gruis NA, Holly EA, Ingvar C, Kanetsky PA, Karagas MR, Le Marchand L,Mackie RM, Olsson H, Østerlind A, Rebbeck TR, Reich K, Sasieni P, Siskind V, Swerdlow AJ, Titus-Ernstoff L, Zens MS, Ziegler A, Barrett JH. A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes. Int J Cancer 2009; 124: 420-428.

Van Gele M., Lambert J. Transport and distribution of melanosomes. In: Borovansky J, Riley PA, editors. Melanins and melanosomes: biosynthesis, biogenesis, physiological and pathological functions. Weinheim: Wiley-VCH Verlag 2011. First Edition. p. 295-322.

Seiberg M. Keratinocyte-melanocyte interactions during melanosome transfer. Pigment Cell Res 2001; 14: 236-242.

Riley PA. Melanin and melanocytes. In: Jarrett A, editor. The physiology and pathophysiology of the skin. London: Academic Press. 1974. Vol 3. p.1104-1130.

Zetterberg A, Killander D. Quantitative cytochemical studies in interphase growth. II Derivation of synthesis curves from the distribution of DNA, RNA mass values of individual mouse fibroblasts in vitro. Exp. Cell Res 1965; 39: 22-32.

Hola M, Riley PA. The relative significance of growth rate and interdivision time in the size control of cultured mammalian epithelial cells. J Cell Sci 1987; 88: 73-80.

Godin M, Delgado FF, Son S, Grover WH, Bryan AK, Tzur A, Jorgensen P, Payer K, Grossman AD, Kirschner MW, Manalis SR. Using buoyant mass to measure growth of single cells. Nat. Methods 2010; 7: 387-390.

Carreira S, Goodall J, Aksan I, La Rocca SA, Galibert M-D, Denat R, Larue L, Godin CR. Mitf cooperates with Rb1 and activates p21 Cip1 expression to regulate cell cycle progression. Nature 2005; 433: 764-769.

Schipany K, Rosner M, Ionce L, Hengstschlager M, Kovacic B. elF3 controls cell size independently of S6K1-activity. Oncotarget 2015.

Lloyd AC. The regulation of cell size. Cell 2013; 154, 1194-1205.

Riley PA. Naevogenesis: a hypothesis concerning the control of proliferation of melanocytes with special reference to the growth of intradermal naevi. Dermatology 1997; 194: 201-204.

SEER Cancer Statistics Factsheets: Melanoma of the Skin. National Cancer Institute. Bethesda, MD, http://seer.cancer. gov/statfacts/html/melan.html

Elwood JM, Jopson J. Melanoma and sun exposure: An overview of published studies. Int J Canc 1997; 73: 198-203.<198::AID-IJC6>3.0.CO;2-R

Stevens NG, Liff JM, Weiss NS. Plantar melanoma: is the incidence of melanoma of the sole of the foot really higher in blacks than whites? Int J Cancer 1990; 45: 691-693.

Ridgeway CA, Hieken TJ, Ronan SG, Kim DK, Das Gupta TK. Acral lentiginous melanoma. Arch Surg 1995; 130: 88-92.

Barnhill RL, Mihm MC Jr. The histopathology of cutaneous malignant melanoma. Semin Diagn Pathol 1993; 10: 47-75.

Halaban R. The regulation of normal melanocyte proliferation. Pigment Cell Res 2000; 13: 4-14.

Rolón PA, Kramárová E, Rolón HI, Khlat M, Parkin DM. Plantar melanoma: a case-control study in Paraguay. Cancer Causes Control 1997; 8: 850-856.

Munyao TM, Othieno-Abinya NA. Cutaneous basal cell carcinoma in Kenya. East Afr Med J 1999; 76: 97-100.

Streutker CJ, McCready D, Jimbow K, From L. Malignant melanoma in a patient with oculocutaneous albinism. J Cutan Med Surg 2000; 4: 149-152.

Parakkal PF. Transfer of premelanosomes into the keratinizing cells of albino hair follicle. J Cell Biol 1967; 35: 473-477.




How to Cite

Patrick A. Riley. (2016). The Influence of Pigment Transfer on the Risk of Developing Melanoma: The Significance of the Melanocyte Amputation Cycle. Journal of Analytical Oncology, 5(3),  87–92.