The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

https://science.sciencemag.org/content/sci/235/4785/177.full.pdf

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

Each of six peptides derived from the human epidermal growth factor (EGF) receptor very closely matches a part of the deduced sequence of the v-erb-B transforming protein of avian erythroblastosis virus (AEV). In all, the peptides contain 83 amino acid residues, 74 of which are shared with v-erb-B. The AEV progenitor may have acquired the cellular gene sequences of a truncated EGF receptor (or closely related protein) lacking the external EGF-binding domain but retaining the transmembrane domain and a domain involved in stimulating cell proliferation. Transformation of cells by AEV may result, in part, from the inappropriate acquisition of a truncated EGF receptor from the c-erb-B gene.

Close similarity of epidermal growth factor receptor and v- erb-B oncogene protein sequences

The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations for neoplastic growth. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not.

https://science.sciencemag.org/content/sci/235/4786/305.full.pdf

The molecular genetics of cancer

Two dozen cellular proto-oncogenes have been discovered to date through the study of retroviruses and the use of gene transfer. They form a structurally and functionally heterogeneous group. At least five distinct mechanisms are responsible for their conversion to active oncogenes. Recent work provides experimental strategies by which many of these oncogenes, as well as oncogenes of DNA tumor viruses, may be placed into functional categories. These procedures may lead to definition of a small number of common pathways through which the various oncogenes act to transform cells.

https://science.sciencemag.org/content/sci/222/4625/771.full.pdf

Cellular Oncogenes and Multistep Carcinogenesis

DEFINITIONS OF CELLULAR ONCOGENES 555 c-one's: The Proto-Oncogenic Progenitors of Retroviral Oncogenes . . . . . . . . . . . . . . . . . . . 555 Identification of Cellular Oncogenes by Functional Tests for Dominant Mutations 558 Using Genetic Rearrangements to Identify Oncogenes . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 Proviral insertions can activate expression oj cellular proto-oncogenes 563 Oncogenes at translocation breakpoints. . ... . . . . ..... 566 Oncogenes in amplified DNA ..... . . ...... ........ . . . ..... ........ . . . .. . . ....... ... . . . . . .. . 567 MOLECULAR PROFILES OF ACTIVATED ONCOGENES 570 Base Substitutions in Mutant ras Alleles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 570 Insertionally Mutated c-myc Loci. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 Locations oj proviruses 574 Additional mutations in proviraUy mutated loci ...... . . .... 576 Characteristics of Other Proviral Insertion Mutations in Proto-Oncogenes 578 Structural and Functional Properties of Translocation Breakpoints near Cellular Oncogenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581 General Jeatures oj c-myc; immunoglobulin gene translocations . . . . . . . . . . . . . . . . . . . . 581 Specific examples of c-myc; Ig translocations in PC and BL lines ........ . . . . . . . . . 583 The Phi chromosome .. . .. ....... . . . . . . . ..... . .. . ... . . . . . . . . ... . . . . . . . ... .. .. .. 586 Other translocations and rearrangements in B cell tumor lines . . . . . . . . . . . . . . . . . . . . . 587 Structural Features oj Amplified Oncogenes . ...... ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587 FROM c-onc TO v-onc: COLLUSION OF MUTATIONAL MECHANISMS....... 588 The Favored Model Jar Transduction of Oncogenes . .. . . 590 The Functional Significance of Diff erences Between c-onc' s and v-onc' s 592 INACTIVATION OF INTEGRATED v-onc GENES: A SAMPLER OF MUTATIONAL MECHANISMS 593

Yuen Kai T Fung

Papers

Activation of the cellular oncogene c-erbB by ltr insertion: Molecular basis for induction of erythroblastosis by avian leukosis virus